|
1
|
Zheng Q, Cui M, Xiao J, Yang S, Chen T, Shi Y, Hu Y, Liao Q. Glycomic profiling of parathyroid neoplasms via lectin microarray analysis. Endocrine 2025; 87:1224-1234. [PMID: 39565545 PMCID: PMC11845408 DOI: 10.1007/s12020-024-04107-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/07/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE Parathyroid carcinoma (PC) is a rare malignancy with a poor prognosis. Diagnosis of PC is often difficult in clinical practice and efficient diagnostic markers are still needed for differential diagnosis. Aberrant glycosylations of glycoproteins were identified with lectin microarray in various cancers, while relevant information is lacking in PC. METHODS In this study, 8 PC and 6 parathyroid adenoma (PA) tissues were assessed using a microarray consisting of 70 lectins. Overall lectin-specific glycosylation patterns were compared between PA and PC tissues. Lectins with significant differential response between PC and PA were further validated by lectin histochemistry. RESULTS The difference in signal intensities was found in 71.4% (50/70) of the lectins between the two groups (P < 0.05). The vast majority of PCs had higher intensity signals than PAs (PCs vs. PAs, ratio >1) and amaranthus caudatus (ACL) showed the most significantly different response between them (ratio = 2.45). Lectin histochemistry further confirmed higher ACL intensity in PCs than in PAs. The differentially expressed glycans in PC tissues were primarily glucose, mannose, and galactose-based. CONCLUSION PC presented unique glycomic features and ACL may serve as a candidate diagnostic marker for PC.
Collapse
Affiliation(s)
- Qingyuan Zheng
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ming Cui
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jinheng Xiao
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Sen Yang
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tianqi Chen
- Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanan Shi
- Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ya Hu
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Quan Liao
- Department of General Surgery, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| |
Collapse
|
|
2
|
Mimura S, Morishita A, Oura K, Takuma K, Nakahara M, Tadokoro T, Fujita K, Tani J, Kobara H. Galectins and Liver Diseases. Int J Mol Sci 2025; 26:790. [PMID: 39859504 PMCID: PMC11766161 DOI: 10.3390/ijms26020790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Galectins are widely distributed throughout the animal kingdom, from marine sponges to mammals. Galectins are a family of soluble lectins that specifically recognize β-galactoside-containing glycans and are categorized into three subgroups based on the number and function of their carbohydrate recognition domains (CRDs). The interaction of galectins with specific ligands mediates a wide range of biological activities, depending on the cell type, tissue context, expression levels of individual galectin, and receptor involvement. Galectins affect various immune cell processes through both intracellular and extracellular mechanisms and play roles in processes, such as apoptosis, angiogenesis, and fibrosis. Their importance has increased in recent years because they are recognized as biomarkers, therapeutic agents, and drug targets, with many other applications in conditions such as cardiovascular diseases and cancer. However, little is known about the involvement of galectins in liver diseases. Here, we review the functions of various galectins and evaluate their roles in liver diseases.
Collapse
Affiliation(s)
- Shima Mimura
- Departments of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Takamatsu 761-0793, Kagawa Prefecture, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
3
|
Mahdavi N, Saffar H, Derakhshan S, Saffar H, Heidari N. Bcl-2 and galectin-3 expression is associated with recurrence of ameloblastoma. Dent Res J (Isfahan) 2024; 21:69. [PMID: 39802810 PMCID: PMC11722749 DOI: 10.4103/drj.drj_706_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 08/21/2024] [Accepted: 09/08/2024] [Indexed: 01/16/2025] Open
Abstract
Background Ameloblastoma is a benign odontogenic neoplasm with a high recurrence rate. Identifying cellular and molecular changes in this neoplasm may help predict the recurrence risk. Bcl-2 and galectin-3 are anti-apoptotic proteins associated with the prognosis of many neoplasms. However, there are a few studies focusing on the association between these two markers and recurrence of ameloblastoma. This study aimed to investigate the association of Bcl-2 plus galectin-3 expression and recurrence of ameloblastoma. Materials and Methods This retrospective cross-sectional study was designed on 48 paraffin-embedded blocks diagnosed as ameloblastoma from 1998 to 2019. We retrieved follow-up data from patients' records and used immunohistochemical staining for Bcl-2 and galectin-3 antibodies. Then, we analyzed their association with recurrence using Chi-square and Mann-Whitney test as well as recurrence-free survival using Kaplan-Meier curves and linear Cox regression. The level of statistical significance was P < 0.05. Results Twenty-six patients had experienced the recurrence. The mean follow-up time was 93.53 months. There was a significant association between Bcl-2 plus cytoplasmic galectin-3 staining and recurrence (both P < 0.001). Furthermore, in univariate analysis, high expression of Bcl-2 was associated with less recurrence-free survival (log-rank: P = 0.020-univariable Cox: P = 0.033), but in multiple Cox regression, there was no significant association (P = 0.471). High cytoplasmic galectin-3 expression was also associated with less recurrence-free survival (log-rank: P = 0.007-univariable Cox: P = 0.015-multiple Cox: P = 0.044). Furthermore, we found a correlation between Bcl-2 and cytoplasmic galectin-3 staining (P = 0.001). Conclusion It seems that Bcl-2 and cytoplasmic galectin-3 staining might predict the risk of ameloblastoma recurrence. However, only the cytoplasmic galectin-3 staining might be an independent predictor of ameloblastoma recurrence, and we recommend further studies.
Collapse
Affiliation(s)
- Nazanin Mahdavi
- Department of Oral and Maxillofacial Pathology, College of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Hana Saffar
- Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Samira Derakhshan
- Department of Oral and Maxillofacial Pathology, College of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Hiva Saffar
- Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Heidari
- Department of Restorative Dentistry, College of Dentistry, Qazvin University of Medical Sciences, Qazvin, Iran
| |
Collapse
|
|
4
|
Ma L, Guo H, Zhao Y, Liu Z, Wang C, Bu J, Sun T, Wei J. Liquid biopsy in cancer current: status, challenges and future prospects. Signal Transduct Target Ther 2024; 9:336. [PMID: 39617822 PMCID: PMC11609310 DOI: 10.1038/s41392-024-02021-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/10/2024] [Accepted: 10/14/2024] [Indexed: 12/06/2024] Open
Abstract
Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.
Collapse
Affiliation(s)
- Liwei Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Huiling Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Yunxiang Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhibo Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Chenran Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Jiahao Bu
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ting Sun
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Jianwei Wei
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
| |
Collapse
|
|
5
|
Chamseddine S, Yavuz BG, Mohamed YI, Lee SS, Yao JC, Hu ZI, LaPelusa M, Xiao L, Sun R, Morris JS, Hatia RI, Hassan M, Duda DG, Diab M, Mohamed A, Nassar A, Amin HM, Kaseb AO. Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma. JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY 2024; 7:255-262. [PMID: 39524465 PMCID: PMC11541930 DOI: 10.36401/jipo-24-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/29/2024] [Accepted: 07/11/2024] [Indexed: 11/16/2024]
Abstract
Introduction Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015). Conclusion Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.
Collapse
Affiliation(s)
- Shadi Chamseddine
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Betul Gok Yavuz
- Department of Internal Medicine, University of Missouri, Columbia, MO, USA
| | - Yehia I. Mohamed
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sunyoung S. Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - James C. Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zishuo Ian Hu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael LaPelusa
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lianchun Xiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ryan Sun
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey S. Morris
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rikita I. Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Manal Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dan G. Duda
- Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Maria Diab
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Ahmed Nassar
- Department of Surgery, Emory University, Atlanta, GA, USA
| | - Hesham M. Amin
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
6
|
Li P, Xie W, Wei H, Yang F, Chen Y, Li Y. Transcriptome Analyses of Liver Sinusoidal Endothelial Cells Reveal a Consistent List of Candidate Genes Associated with Endothelial Dysfunction and the Fibrosis Progression. Curr Issues Mol Biol 2024; 46:7997-8014. [PMID: 39194690 DOI: 10.3390/cimb46080473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/21/2024] [Accepted: 07/23/2024] [Indexed: 08/29/2024] Open
Abstract
Liver fibrosis is an important step in the transformation of chronic liver disease into cirrhosis and liver cancer, and structural changes and functional disorders of liver sinusoidal endothelial cells (LSECs) are early events in the occurrence of liver fibrosis. Therefore, it is necessary to identify the key regulatory genes of endothelial dysfunction in the process of liver fibrosis to provide a reference for the diagnosis and treatment of liver fibrosis. In this study, we identified 230 common differentially expressed genes (Co-DEGs) by analyzing transcriptomic data of primary LSECs from three different liver fibrosis mouse models (carbon tetrachloride; choline-deficient, l-amino acid-defined diet; and nonalcoholic steatohepatitis). Enrichment analysis revealed that the Co-DEGs were mainly involved in regulating the inflammatory response, immune response, angiogenesis, formation and degradation of the extracellular matrix, and mediating chemokine-related pathways. A Venn diagram analysis was used to identify 17 key genes related to the progression of liver cirrhosis. Regression analysis using the Lasso-Cox method identified genes related to prognosis among these key genes: SOX4, LGALS3, SERPINE2, CD52, and LPXN. In mouse models of liver fibrosis (bile duct ligation and carbon tetrachloride), all five key genes were upregulated in fibrotic livers. This study identified key regulatory genes for endothelial dysfunction in liver fibrosis, namely SOX4, LGALS3, SERPINE2, CD52, and LPXN, which will provide new targets for the development of therapeutic strategies targeting endothelial dysfunction in LSECs and liver fibrosis.
Collapse
Affiliation(s)
- Penghui Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Wenjie Xie
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Hongjin Wei
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Fan Yang
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Yan Chen
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Yinxiong Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangzhou 510530, China
| |
Collapse
|
|
7
|
Chen Y, Zhang W, Cheng M, Hao X, Wei H, Sun R, Tian Z. Galectin-3-ITGB1 Signaling Mediates Interleukin 10 Production of Hepatic Conventional Natural Killer Cells in Hepatitis B Virus Transgenic Mice and Correlates with Hepatocellular Carcinoma Progression in Patients. Viruses 2024; 16:737. [PMID: 38793619 PMCID: PMC11125742 DOI: 10.3390/v16050737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 04/30/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND AND AIMS The outcomes of HBV infections are related to complex immune imbalances; however, the precise mechanisms by which HBV induces immune dysfunction are not well understood. METHODS HBV transgenic (HBs-Tg) mice were used to investigate intrahepatic NK cells in two distinct subsets: conventional NK (cNK) and liver-resident NK (LrNK) cells during a chronic HBV infection. RESULTS The cNK cells, but not the LrNK cells, were primarily responsible for the increase in the number of bulk NK cells in the livers of ageing HBs-Tg mice. The hepatic cNK cells showed a stronger ability to produce IL-10, coupled with a higher expression of CD69, TIGIT and PD-L1, and lower NKG2D expression in ageing HBs-Tg mice. A lower mitochondrial mass and membrane potential, and less polarized localization were observed in the hepatic cNK cells compared with the splenic cNK cells in the HBs-Tg mice. The enhanced galectin-3 (Gal-3) secreted from HBsAg+ hepatocytes accounted for the IL-10 production of hepatic cNK cells via ITGB1 signaling. For humans, LGALS3 and ITGB1 expression is positively correlated with IL-10 expression, and negatively correlated with the poor clinical progression of HCC. CONCLUSIONS Gal-3-ITGB1 signaling shapes hepatic cNK cells but not LrNK cells during a chronic HBV infection, which may correlate with HCC progression.
Collapse
Affiliation(s)
- Yongyan Chen
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
- Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China
| | - Wendi Zhang
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
| | - Min Cheng
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
- Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
| | - Xiaolei Hao
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
| | - Haiming Wei
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
- Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China
| | - Rui Sun
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
- Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China
| | - Zhigang Tian
- Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
- Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China
| |
Collapse
|
|
8
|
Ren Y, Qian Y, Zhang Q, Li X, Li M, Li W, Yang P, Ren H, Li H, Weng Y, Li D, Xu K, Yu W. High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma. Cancer Cell Int 2024; 24:142. [PMID: 38643145 PMCID: PMC11031979 DOI: 10.1186/s12935-024-03309-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 03/22/2024] [Indexed: 04/22/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. METHODS In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. RESULTS First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. CONCLUSIONS Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.
Collapse
Affiliation(s)
- Yinghui Ren
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Yongmei Qian
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Qicheng Zhang
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Xiaoping Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Mingjiang Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Wei Li
- Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Pan Yang
- Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Hengchang Ren
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Hongxia Li
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Yiqi Weng
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Dengwen Li
- College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Ke Xu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
| | - Wenli Yu
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300192, China.
| |
Collapse
|
|
9
|
Perez-Moreno E, Oyanadel C, de la Peña A, Hernández R, Pérez-Molina F, Metz C, González A, Soza A. Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis. Biol Res 2024; 57:14. [PMID: 38570874 PMCID: PMC10993482 DOI: 10.1186/s40659-024-00490-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 03/12/2024] [Indexed: 04/05/2024] Open
Abstract
Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids and modulate a broad spectrum of physiological and pathological processes. The expression and subcellular localization of different galectins vary among tissues and cell types and change during processes of tissue repair, fibrosis and cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) that occurs in the context of these processes can include modifications of glycosylation patterns of glycolipids and glycoproteins affecting their interactions with galectins. Moreover, overexpression of certain galectins has been involved in the development and different outcomes of EMT. This review focuses on the roles and mechanisms of Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 and Gal-8, which have been involved in physiologic and pathogenic EMT contexts.
Collapse
Affiliation(s)
- Elisa Perez-Moreno
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
- Centro Científico y Tecnológico de Excelencia (CCTE) Ciencia y Vida, Santiago, Chile
| | - Claudia Oyanadel
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
- Departamento de Ciencias Biológicas y Químicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
| | - Adely de la Peña
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
- Centro Científico y Tecnológico de Excelencia (CCTE) Ciencia y Vida, Santiago, Chile
| | - Ronny Hernández
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
| | - Francisca Pérez-Molina
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
| | - Claudia Metz
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
| | - Alfonso González
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
- Centro Científico y Tecnológico de Excelencia (CCTE) Ciencia y Vida, Santiago, Chile.
| | - Andrea Soza
- Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
- Centro Científico y Tecnológico de Excelencia (CCTE) Ciencia y Vida, Santiago, Chile.
| |
Collapse
|
|
10
|
Mackinnon AC, Tonev D, Jacoby B, Pinzani M, Slack RJ. Galectin-3: therapeutic targeting in liver disease. Expert Opin Ther Targets 2023; 27:779-791. [PMID: 37705214 DOI: 10.1080/14728222.2023.2258280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 09/08/2023] [Indexed: 09/15/2023]
Abstract
INTRODUCTION The rising incidence of liver diseases is a worldwide healthcare concern. However, the therapeutic options to manage chronic inflammation and fibrosis, the processes at the basis of morbidity and mortality of liver diseases, are very limited. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs. Several Gal-3 inhibitors are currently in clinical development. AREAS COVERED This review describes our current understanding of the role of Gal-3 in chronic liver diseases, with special emphasis on fibrosis. Also, we review therapeutic advances based on Gal-3 inhibition, describing drug properties and their current status in clinical research. EXPERT OPINION Currently, the known effects of Gal-3 point to a direct activation of the NLRP3 inflammasome leading to its activation in liver macrophages and activated macrophages play a key role in tissue fibrogenesis. However, more research is needed to elucidate the role of Gal-3 in the different activation pathways, dissecting the intracellular and extracellular mechanisms of Gal-3, and its role in pathogenesis. Gal-3 could be a target for early therapy of numerous hepatic diseases and, given the lack of therapeutic options for liver fibrosis, there is a strong pharmacologic potential for Gal-3-based therapies.
Collapse
Affiliation(s)
| | - Dimitar Tonev
- Galecto Biotech AB, Cobis Science Park, Copenhagen, Denmark
| | - Brian Jacoby
- Galecto Biotech AB, Cobis Science Park, Copenhagen, Denmark
| | - Massimo Pinzani
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Robert J Slack
- Galecto Biotech AB, Cobis Science Park, Copenhagen, Denmark
| |
Collapse
|
|
11
|
Li S, Pritchard DM, Yu LG. Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells. Cell Death Dis 2023; 14:268. [PMID: 37055381 PMCID: PMC10102123 DOI: 10.1038/s41419-023-05789-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 03/28/2023] [Accepted: 03/31/2023] [Indexed: 04/15/2023]
Abstract
Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/β signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.
Collapse
Affiliation(s)
- Shun Li
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - David Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Lu-Gang Yu
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
| |
Collapse
|
|
12
|
Lima T, Perpétuo L, Henrique R, Fardilha M, Leite-Moreira A, Bastos J, Vitorino R. Galectin-3 in prostate cancer and heart diseases: a biomarker for these two frightening pathologies? Mol Biol Rep 2023; 50:2763-2778. [PMID: 36583779 PMCID: PMC10011345 DOI: 10.1007/s11033-022-08207-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/13/2022] [Indexed: 12/31/2022]
Abstract
Galectin-3 (Gal-3) belongs to galectin protein family, a type of β-galactose-binding lectin having more than one evolutionarily conserved domain of carbohydrate recognition. Gal-3 is mainly located in the cytoplasm, but it also enters the nucleus and is secreted into the extracellular environment and biological fluids such as urine, saliva, and serum. It plays an important role in many biological functions, such as angiogenesis, apoptosis, cell differentiation, cell growth, fibrosis, inflammation, host defense, cellular modification, splicing of pre-mRNA, and transformation. Many previous studies have shown that Gal-3 can be used as a diagnostic or prognostic biomarker for heart ailments, kidney diseases, and other major illnesses including cancer. Moreover, it may also play a major role in risk stratification in different diseases, and in this review, we have summarized the potential roles and application of Gal-3 as diagnostic, prognostic, and risk stratifying biomarker from previously reported studies in heart diseases and cancer, with special emphasis on prostate cancer.
Collapse
Affiliation(s)
- Tânia Lima
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
| | - Luís Perpétuo
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, UnIC, Porto, Portugal
| | - Rui Henrique
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira, 228, 4050‑313, Porto, Portugal
| | - Margarida Fardilha
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Adelino Leite-Moreira
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, UnIC, Porto, Portugal
| | - Jose Bastos
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Rui Vitorino
- iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
- Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, UnIC, Porto, Portugal
- LAQV-REQUIMTE, Departamento de Química, Universidade de Aveiro, Aveiro, Portugal
- Department of Chemistry, University of Aveiro, Aveiro, Portugal
| |
Collapse
|
|
13
|
Implications of Transglutaminase-Mediated Protein Serotonylation in the Epigenetic Landscape, Small Cell Lung Cancer, and Beyond. Cancers (Basel) 2023; 15:cancers15041332. [PMID: 36831672 PMCID: PMC9954789 DOI: 10.3390/cancers15041332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/08/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023] Open
Abstract
In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own do not appear to be particularly effective, suggesting that there may be other regulatory parameters that dictate the effectiveness of vorinostat's reversal of histone deacetylation. Recent discoveries that serotonylation of histone H3 alters the permissibility of gene expression have led to renewed attention to this rare modification, as facilitated by transglutaminase 2, and at the same time introduce new questions about whether this modification belongs to a part of the concerted cohort of regulator events for modulating the epigenetic landscape. This review explores the mechanistic details behind protein serotonylation and its possible connections to the epigenome via histone modifications and glycan interactions and attempts to elucidate the role of transglutaminase 2, such that optimizations to existing histone deacetylase inhibitor designs or combination therapies may be devised for lung and other types of cancer.
Collapse
|
|
14
|
Al-Maghrabi JA, Khabaz MN. Clinical significance of galectin-3 expression in urinary bladder carcinoma. J Int Med Res 2023; 51:3000605231153323. [PMID: 36748414 PMCID: PMC9909066 DOI: 10.1177/03000605231153323] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To uncover the clinical significance of galectin-3 in the evolution of urinary bladder cancer by defining galectin-3 expression and examining the relationship between its expression in a group of urothelial carcinomas versus normal tissues along with clinicopathological factors. METHODS This retrospective study included histopathological reports and archival blocks and slides of all patients with urinary bladder cancer treated at King Abdulaziz University Hospital (Jeddah, Saudi Arabia). An anti-galectin-3 monoclonal antibody was used for immunohistochemical staining of tissue microarray slides comprising 128 cases of urothelium carcinoma and 24 specimens of normal bladder mucosa. RESULTS Galectin-3 was downregulated during transformation, with positive expression found in 50 (39%) urinary bladder neoplasms, of which 33 (66%) showed weak immunostaining. All positively-stained malignant tumor and normal bladder mucosa samples showed cytoplasmic staining; a few samples also showed nuclear staining. No correlation was noted between galectin-3 and histotype, grade, stage, muscularis propria invasion, lymph node invasion, vascular invasion, or metastasis. A Cox proportional hazards model and Kaplan-Meier survival curves did not show differences in survival on the basis of galectin-3 expression. CONCLUSION Galectin-3 is down-regulated in bladder cancer but is not a helpful marker for the diagnosis or prognosis of urinary bladder cancer.
Collapse
Affiliation(s)
- Jaudah Ahmed Al-Maghrabi
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia,King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia
| | - Mohamad Nidal Khabaz
- Department of Pathology, Rabigh Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia,Mohamad Nidal Khabaz, Department of Pathology, Rabigh Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
| |
Collapse
|
|
15
|
Ezhilarasan D. Unraveling the pathophysiologic role of galectin-3 in chronically injured liver. J Cell Physiol 2023; 238:673-686. [PMID: 36745560 DOI: 10.1002/jcp.30956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 01/04/2023] [Accepted: 01/12/2023] [Indexed: 02/07/2023]
Abstract
Galectin-3 (Gal-3) previously referred to as S-type lectins, is a soluble protein that specifically binds to β-galactoside carbohydrates with high specificity. Gal-3 plays a pivotal role in a variety of pathophysiological processes such as cell proliferation, inflammation, differentiation, angiogenesis, transformation and apoptosis, pre-mRNA splicing, metabolic syndromes, fibrosis, and host defense. The role of Gal-3 has also been implicated in liver diseases. Gal-3 is activated upon a hepatotoxic insult to the liver and its level has been shown to be upregulated in fatty liver diseases, inflammation, nonalcoholic steatohepatitis, fibrosis, cholangitis, cirrhosis, and hepatocellular carcinoma (HCC). Gal-3 directly interacts with the NOD-like receptor family, pyrin domain containing 3, and activates the inflammasome in macrophages of the liver. In the chronically injured liver, Gal-3 secreted by injured hepatocytes and immune cells, activates hepatic stellate cells (HSCs) in a paracrine fashion to acquire a myofibroblast like collagen-producing phenotype. Activated HSCs in the fibrotic liver secrete Gal-3 which acts via autocrine signaling to exacerbate extracellular matrix synthesis and fibrogenesis. In the stromal microenvironment, Gal-3 activates cancer cell proliferation, migration, invasiveness, and metastasis. Clinically, increased serum levels and Gal-3 expression were observed in the liver tissue of nonalcoholic steatohepatitis, fibrotic/cirrhotic, and HCC patients. The pathological role of Gal-3 has been experimentally and clinically reported in the progression of chronic liver disease. Therefore, this review discusses the pathological role of Gal-3 in the progression of chronic liver diseases.
Collapse
Affiliation(s)
- Devaraj Ezhilarasan
- Department of Pharmacology, Molecular Medicine and Toxicology Lab, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| |
Collapse
|
|
16
|
Li D, Jia S, Wang S, Hu L. Glycoproteomic Analysis of Urinary Extracellular Vesicles for Biomarkers of Hepatocellular Carcinoma. Molecules 2023; 28:molecules28031293. [PMID: 36770959 PMCID: PMC9919939 DOI: 10.3390/molecules28031293] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/21/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the most common form of primary liver cancer cases and constitutes a major health problem worldwide. The diagnosis of HCC is still challenging due to the low sensitivity and specificity of the serum α-fetoprotein (AFP) diagnostic method. Extracellular vesicles (EVs) are heterogeneous populations of phospholipid bilayer-enclosed vesicles that can be found in many biological fluids, and have great potential as circulating biomarkers for biomarker discovery and disease diagnosis. Protein glycosylation plays crucial roles in many biological processes and aberrant glycosylation is a hallmark of cancer. Herein, we performed a comprehensive glycoproteomic profiling of urinary EVs at the intact N-glycopeptide level to screen potential biomarkers for the diagnosis of HCC. With the control of the spectrum-level false discovery rate ≤1%, 756 intact N-glycopeptides with 154 N-glycosites, 158 peptide backbones, and 107 N-glycoproteins were identified. Out of 756 intact N-glycopeptides, 344 differentially expressed intact N-glycopeptides (DEGPs) were identified, corresponding to 308 upregulated and 36 downregulated N-glycopeptides, respectively. Compared to normal control (NC), the glycoproteins LG3BP, PIGR and KNG1 are upregulated in HCC-derived EVs, while ASPP2 is downregulated. The findings demonstrated that specific site-specific glycoforms in these glycoproteins from urinary EVs could be potential and efficient non-invasive candidate biomarkers for HCC diagnosis.
Collapse
Affiliation(s)
- Dejun Li
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China
- Prenatal Diagnosis Center, Reproductive Medicine Center, The First Hospital of Jilin University, Changchun 130021, China
| | - Shengnan Jia
- Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun 130041, China
- Correspondence: (S.J.); (L.H.)
| | - Shuyue Wang
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China
| | - Lianghai Hu
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China
- Correspondence: (S.J.); (L.H.)
| |
Collapse
|
|
17
|
The Synthesis and Preclinical Investigation of Lactosamine-Based Radiopharmaceuticals for the Detection of Galectin-3-Expressing Melanoma Cells. Pharmaceutics 2022; 14:pharmaceutics14112504. [PMID: 36432695 PMCID: PMC9695418 DOI: 10.3390/pharmaceutics14112504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/04/2022] [Accepted: 11/15/2022] [Indexed: 11/19/2022] Open
Abstract
Given that galectin-3 (Gal-3) is a β-galactoside-binding lectin promoting tumor growth and metastatis, it could be a valuable target for the treatment of Gal-3-expressing neoplasms. An aromatic group introduced to the C-3′ position of lactosamine increased its affinity for Gal-3. Herein, we aimed at developing a radiopharmaceutical for the detection of Gal-3 positive malignancies. To enhance tumor specificity, a heterodimeric radiotracer capable of binding to both Gal-3 and αvβ3 integrin was also synthetized. Arginine-glycine-asparagine (RGD) peptide is the ligand of angiogenesis- and metastasis-associated αvβ3 integrin. Following the synthesis of the chelator-conjugated (2-naphthyl)methylated lactosamine, the obtained compound was applied as a precursor for radiolabeling and was conjugated to the RGD peptide by click reaction as well. Both synthetized precursors were radiolabeled with 68Ga, resulting in high labeling yield (>97). The biological studies were carried out using B16F10 melanoma tumor-bearing C57BL6 mice. High tumor accumulation of both labeled lactosamine derivatives—detected by in vivo PET and ex vivo biodistribution studies—indicated their potential for melanoma detection. However, the heterodimer radiotracer showed high hepatic uptake, while low liver accumulation characterized chelator-conjugated lactosamine, resulting in PET images with excellent contrast. Therefore, this novel carbohydrate-based radiotracer is suitable for the highly selective determination of Gal-3-expressing melanoma cells.
Collapse
|
|
18
|
Zanotti S, Boot GF, Coto-Llerena M, Gallon J, Hess GF, Soysal SD, Kollmar O, Ng CKY, Piscuoglio S. The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective. Front Med (Lausanne) 2022; 9:888850. [PMID: 35814741 PMCID: PMC9263082 DOI: 10.3389/fmed.2022.888850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 05/23/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) typically develops from a background of cirrhosis resulting from chronic inflammation. This inflammation is frequently associated with chronic liver diseases (CLD). The advent of next generation sequencing has enabled extensive analyses of molecular aberrations in HCC. However, less attention has been directed to the chronically inflamed background of the liver, prior to HCC emergence and during recurrence following surgery. Hepatocytes within chronically inflamed liver tissues present highly activated inflammatory signaling pathways and accumulation of a complex mutational landscape. In this altered environment, cells may transform in a stepwise manner toward tumorigenesis. Similarly, the chronically inflamed environment which persists after resection may impact the timing of HCC recurrence. Advances in research are allowing an extensive epigenomic, transcriptomic and proteomic characterization of CLD which define the emergence of HCC or its recurrence. The amount of data generated will enable the understanding of oncogenic mechanisms in HCC from the CLD perspective and provide the possibility to identify robust biomarkers or novel therapeutic targets for the treatment of primary and recurrent HCC. Importantly, biomarkers defined by the analysis of CLD tissue may permit the early detection or prevention of HCC emergence and recurrence. In this review, we compile the current omics based evidence of the contribution of CLD tissues to the emergence and recurrence of HCC.
Collapse
Affiliation(s)
- Sofia Zanotti
- Anatomic Pathology Unit, IRCCS Humanitas University Research Hospital, Milan, Italy
| | - Gina F. Boot
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Mairene Coto-Llerena
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
- Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | - John Gallon
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Gabriel F. Hess
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Savas D. Soysal
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Otto Kollmar
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Charlotte K. Y. Ng
- Department for BioMedical Research, University of Bern, Bern, Switzerland
- Swiss Institute of Bioinformatics, Lausanne, Switzerland
- Bern Center for Precision Medicine, Bern, Switzerland
| | - Salvatore Piscuoglio
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
- Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
- *Correspondence: Salvatore Piscuoglio
| |
Collapse
|
|
19
|
Yang JC, Hu JJ, Li YX, Luo W, Liu JZ, Ye DW. Clinical Applications of Liquid Biopsy in Hepatocellular Carcinoma. Front Oncol 2022; 12:781820. [PMID: 35211399 PMCID: PMC8860830 DOI: 10.3389/fonc.2022.781820] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognosis in the world. The low rate of early diagnosis, as well as the high risk of postoperative metastasis and recurrence, led to the poor clinical prognosis of HCC patients. Currently, it mainly depends on serum markers, imaging examination, and tissue biopsy to diagnose and determine the recurrence and metastasis of HCC after treatments. Nevertheless, the accuracy and sensitivity of serum markers and imaging for early HCC diagnosis are suboptimal. Tissue biopsy, containing limited tissue samples, is insufficient to reveal comprehensive tumor biology information and is inappropriate to monitor dynamic tumor progression due to its invasiveness. Thus, low invasive diagnostic methods and novel biomarkers with high sensitivity and reliability must be found to improve HCC detection and prediction. As a non-invasive, dynamic, and repeatable detection method, “liquid biopsy”, has attracted much attention to early diagnosis and monitoring of treatment response, which promotes the progress of precision medicine. This review summarizes the clinical applications of liquid biopsy in HCC, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosome in early diagnosis, prognostic evaluation, disease monitoring, and guiding personalized treatment.
Collapse
Affiliation(s)
- Jin-Cui Yang
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun-Jie Hu
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi-Xin Li
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Luo
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-Zhou Liu
- Department of Pain Management, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Da-Wei Ye
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Pancreatic-Biliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| |
Collapse
|
|
20
|
A Novel Hypoxic-Angiogenesis-Immune-Related Gene Model for Prognostic and Therapeutic Effect Prediction in Hepatocellular Carcinoma Patients. DISEASE MARKERS 2022; 2022:9428660. [PMID: 35069936 PMCID: PMC8769836 DOI: 10.1155/2022/9428660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/07/2021] [Indexed: 12/04/2022]
Abstract
Background Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignant tumors that have been discovered so far, which makes the prognostic prediction difficult. The hypoxia, angiogenesis, and immunity-related genes (HAIRGs) are closely related to the development of liver cancer. However, the prognostic and treatment effect of hypoxia, angiogenesis, and immunity-related genes in HCC continues to be further clarified. Methods The gene expression quantification data and clinical information in patients with liver cancer were downloaded from the TCGA database, and HAIRG signature was built by using the least absolute shrinkage and selection operator (LASSO) technique. Patient from the ICGC database validated the model. Then, tumor immune dysfunction and exclusion (TIDE) algorithm was applied to estimate the clinical response to immunotherapy and the sensitivity of drugs was evaluated by the half-maximal inhibitory concentration (IC50). Result The HAIRGs were identified between the HCC patients and normal patients in the TCGA database. In univariate Cox regression analysis, seventeen differentially expressed genes (DEGs) were associated with overall survival (OS). An eight HAIRG signature model was constructed and was used to divide the patients into two groups according to the median value of the risk score base on the TCGA dataset. Patients in the high-risk group had a significant reduction in OS compared to those in the low-risk group (P < 0.001 in the TCGA, P < 0.001 in the ICGC). For TCGA and ICGC databases of univariate Cox regression analyses, the risk score was used as an independent predictor of OS (HR > 1, P < 0.001). Functional analysis showed that the relevant immune pathways and immune responses were enriched, cellular component analysis showed that the immunoglobulin complex and other related substances were enriched, and immune status existed a difference in the high- and low-risk groups. Then, the tumor immune dysfunction and exclusion (TIDE) algorithm presented differences in immune response in the high- and low-risk groups (P < 0.05), and based on drug sensitivity prediction, patients in the high-risk group were more sensitive to cisplatin compared to those in the low-risk group in both the TCGA and ICGC cohorts (P < 0.05). Conclusions HAIRG signature can be utilized for prognostic prediction in HCC, while it can be considered a prediction model for clinical evaluation of immunotherapy response and chemotherapy sensitivity in HCC.
Collapse
|
|
21
|
Scheiter A, Evert K, Reibenspies L, Cigliano A, Annweiler K, Müller K, Pöhmerer LMG, Xu H, Cui G, Itzel T, Materna-Reichelt S, Coluccio A, Honarnejad K, Teufel A, Brochhausen C, Dombrowski F, Chen X, Evert M, Calvisi DF, Utpatel K. RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues. Mol Oncol 2021; 16:1091-1118. [PMID: 34748271 PMCID: PMC8895452 DOI: 10.1002/1878-0261.13135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/19/2021] [Accepted: 11/04/2021] [Indexed: 02/05/2023] Open
Abstract
Aberrant activation of the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and Ras/mitogen‐activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain‐containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild‐type mice by hydrodynamic tail vein injection combined with sleeping beauty‐mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl‐CoA desaturase‐1 (SCD1). Galectin‐1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co‐inhibitory treatment with PIK3CA inhibitors and the galectin‐1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.
Collapse
Affiliation(s)
| | - Katja Evert
- Institute of Pathology, University of Regensburg, Germany
| | | | | | | | - Karolina Müller
- Center for Clinical Studies, University Hospital Regensburg, Germany
| | | | - Hongwei Xu
- Department of Liver Surgery, Center of Liver Transplantation, West China Hospital of Sichuan University, Chengdu, China.,Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA
| | - Guofei Cui
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA
| | - Timo Itzel
- Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Silvia Materna-Reichelt
- Division of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany
| | - Andrea Coluccio
- Division of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany
| | - Kamran Honarnejad
- Division of Personalized Tumor Therapy, Fraunhofer Institute for Toxicology and Experimental Medicine, Regensburg, Germany
| | - Andreas Teufel
- Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | | | - Frank Dombrowski
- Institute of Pathology, University Medicine of Greifswald, Germany
| | - Xin Chen
- Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA
| | - Matthias Evert
- Institute of Pathology, University of Regensburg, Germany
| | | | | |
Collapse
|
|
22
|
An Y, Xu S, Liu Y, Xu X, Philips CA, Chen J, Méndez-Sánchez N, Guo X, Qi X. Role of Galectins in the Liver Diseases: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:744518. [PMID: 34778306 PMCID: PMC8578830 DOI: 10.3389/fmed.2021.744518] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 09/22/2021] [Indexed: 02/05/2023] Open
Abstract
Background: Galectins, a family of β-galactoside-binding proteins, are related to the development and progression of various human diseases such as cancer, heart failure, and chronic kidney disease. However, its role in liver diseases is unclear. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Hazard ratios (HRs), odds ratios (ORs), and mean differences (MDs) with 95% CIs were pooled to evaluate the association of the galectins with the outcomes and risk of liver diseases by a random effects model. Results: Thirty three studies involving 43 cohorts and 4,168 patients with liver diseases were included. In the patients with hepatocellular carcinoma (HCC), high expression of galectin-1 and -3 in the tissues was significantly associated with worse overall survival (galectin-1: HR = 1.94, 95% CI = 1.61-2.34, p < 0.001; galectin-3: HR = 3.29, 95% CI = 1.62-6.68, p < 0.001) and positive vascular invasion (galectin-1: OR = 1.74, 95% CI = 1.18-2.58, p = 0.005; galectin-3: OR = 2.98, 95% CI = 1.58-5.60, p = 0.001); but, high expression of galectin-4 and -9 in the tissues was significantly associated with better overall survival (galectin-4: HR = 0.53, 95% CI = 0.36-0.79, p = 0.002; galectin-9: HR = 0.56, 95% CI = 0.44-0.71, p < 0.001) and negative vascular invasion (galectin-4: OR = 0.36, 95% CI = 0.19-0.72, p = 0.003; galectin-9: OR = 0.60, 95% CI = 0.37-0.97, p = 0.037). Serum galectin-3 level was significantly higher in HCC (MD = 3.06, 95% CI = 1.79-4.32, p < 0.001), liver failure (MD = 0.44, 95% CI = 0.23-0.66, p < 0.001), liver cirrhosis (MD = 1.83, 95% CI = 1.15-2.51, p < 0.001), and chronic active hepatitis B (MD = 18.95, 95% CI = 10.91-27.00, p < 0.001); serum galectin-9 level was significantly higher in HCC (MD = 3.74, 95% CI = 2.57-4.91, p < 0.001) and autoimmune hepatitis (MD = 8.80, 95% CI = 7.61-9.99, p < 0.001). Conclusion: High galectin-1 and -3 and low galectin-4 and -9 expression indicate worse outcomes of patients with HCC. Serum galectin-3 and -9 levels are positively associated with the risk of chronic liver diseases.
Collapse
Affiliation(s)
- Yang An
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
| | - Shixue Xu
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Yiting Liu
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Physical Examination Center, The First Affiliated Hospital, China Medical University, Shenyang, China
| | - Xiangbo Xu
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China
| | - Cyriac Abby Philips
- The Liver Unit and Monarch Liver Laboratory, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi, India
| | - Jiang Chen
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Xiaozhong Guo
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xingshun Qi
- Meta-Analysis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| |
Collapse
|
|
23
|
Xing M, Wang X, Kiken RA, He L, Zhang JY. Immunodiagnostic Biomarkers for Hepatocellular Carcinoma (HCC): The First Step in Detection and Treatment. Int J Mol Sci 2021; 22:6139. [PMID: 34200243 PMCID: PMC8201127 DOI: 10.3390/ijms22116139] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) exerts huge effects on the health burden of the world because of its high mortality and poor prognosis. HCC is often clinically detected late in patients. If HCC could be detected and treated earlier, the survival rate of patients will be greatly improved. Therefore, identifying specific biomarkers is urgent and important for HCC. The liver is also recognized as an immune organ. The occurrence of HCC is related to exacerbation of immune tolerance and/or immunosurveillance escape. The host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy, as can be seen from the clinical success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells. Thus, there is a pressing medical need to discover immunodiagnostic biomarkers specific to HCC for understanding the pathological mechanisms of HCC, especially for immunotherapy targets. We have reviewed the existing literature to summarize the immunodiagnostic markers of HCC, including autoantibodies against tumor-associated antigens (TAAs) and exosomes, to provide new insights into HCC and early detection of this deadly cancer.
Collapse
Affiliation(s)
- Mengtao Xing
- Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China;
- Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA; (X.W.); (R.A.K.)
| | - Xinzhi Wang
- Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA; (X.W.); (R.A.K.)
- Jiangsu Key Laboratory of Drug Screening, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China
| | - Robert A. Kiken
- Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA; (X.W.); (R.A.K.)
| | - Ling He
- Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China;
| | - Jian-Ying Zhang
- Department of Biological Sciences & NIH-Sponsored Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA; (X.W.); (R.A.K.)
| |
Collapse
|
|
24
|
Comparison between galectin-3 and YKL-40 levels for the assessment of liver fibrosis in cirrhotic patients. Arab J Gastroenterol 2021; 22:187-192. [PMID: 34088622 DOI: 10.1016/j.ajg.2021.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 02/22/2021] [Accepted: 03/29/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND STUDY AIMS The circulatory levels of Galectin-3 and YKL-40 are considered as candidate biomarkers for the noninvasive assessment of liver fibrosis. This study aimed to evaluate the plasma protein profiles of Galectin-3 and YKL-40 in patients with cirrhosis (with and without hepatocellular carcinoma [HCC]) who underwent deceased-donor liver transplantation (LT), before and after surgery. PATIENTS AND METHODS The plasma levels of Galectin-3 and YKL-40 were assessed in 46 subjects, including 24 liver graft recipients (before, 1 day after, and 1 month after LT) and 22 healthy controls using enzyme-linked immunosorbent assays. RESULTS The levels of Galectin-3 and YKL-40 in the LT recipients before the transplant were significantly higher than those in the healthy controls (p < 0.001 and p < 0.01, respectively). YKL-40 levels returned to normal within 1 day after LT, whereas those of Galectin-3 decreased 1 day after LT and returned to normal levels after 1 month. The levels of both proteins did not differ between patients with and without HCC. Unlike YKL-40, the pre-transplant levels of Galectin-3 were directly correlated to that of aspartate aminotransferase (AST; r = 0.473, p = 0.01), alanine aminotransferase (r = 0.395, p = 0.04), total bilirubin (r = 0.545, p = 0.003), and lactate dehydrogenase (r = 0.452, p = 0.02) and to the AST to platelet ratio index (APRI; r = 0.411, p = 0.03) and Child-Pugh score (r = 0.601, p < 0.001). Galectin-3 levels increased significantly according to the severity of cirrhosis (25.9 ± 2.7; 57.4 ± 29.6; and 81 ± 27 ng/mL in Class A, B, and C cirrhosis, respectively), whereas those of YKL-40 tended to be higher in the Class C patients compared to the Class A patients (8.9 ± 2.6 vs. 7.4 ± 0.8 ng/mL). CONCLUSION Circulating levels of Galectin-3 could be an indicator of liver damage and inflammation that are correlated with fibrosis.
Collapse
|
|
25
|
Galectin-3 is not useful for hepatocellular carcinoma surveillance in cirrhotic patients but it may be a marker of cirrhosis development. Clin Exp Hepatol 2021; 7:74-78. [PMID: 34027118 PMCID: PMC8122102 DOI: 10.5114/ceh.2021.104385] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/20/2020] [Indexed: 12/11/2022] Open
Abstract
Aim of the study Ultrasound surveillance for hepatocellular carcinoma (HCC) among cirrhotic patients is the currently used modality but it is operator dependent. Combining a tumor marker with ultrasound may improve sensitivity for early HCC detection. Our aim was to assess the galectin-3 level among HCC and cirrhotic patients on top of chronic hepatitis C to evaluate its possible role as a tumor marker for HCC surveillance among cirrhotic patients. Material and methods The study was conducted on 160 subjects. They were grouped as follows: group 1: 40 patients with HCC secondary to liver cirrhosis on top of chronic hepatitis C; group 2: 40 patients with cirrhosis secondary to chronic hepatitis C; group 3: 40 patients with chronic hepatitis C without advanced fibrosis; group 4: 40 healthy controls. Serum galectin-3 levels were determined in all subjects using ELISA. Results Serum galectin-3 level was significantly higher in HCC patients than in those with chronic hepatitis C (p < 0.001). Also it was significantly higher among cirrhotic patients than in patients with chronic hepatitis C (p < 0.001). But on comparing HCC patients with cirrhotic patients, serum galectin-3 levels were not significantly different (p = 0.926). Conclusions: Galectin-3 levels cannot be used as an additional method for surveillance of HCC among cirrhotic patients.
Collapse
|
|
26
|
Sturgill ER, Rolig AS, Linch SN, Mick C, Kasiewicz MJ, Sun Z, Traber PG, Shlevin H, Redmond WL. Galectin-3 inhibition with belapectin combined with anti-OX40 therapy reprograms the tumor microenvironment to favor anti-tumor immunity. Oncoimmunology 2021; 10:1892265. [PMID: 33717655 PMCID: PMC7927986 DOI: 10.1080/2162402x.2021.1892265] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Treatment with an agonist anti-OX40 antibody (aOX40) boosts anti-tumor immunity by providing costimulation and driving effector T cell responses. However, tumor-induced immune suppression contributes significantly to poor response rates to aOX40 therapy, thus combining aOX40 with other agents that relieve tumor-mediated immune suppression may significantly improve outcomes. Once such target is galectin-3 (Gal-3), which drives tumor-induced immunosuppression by increasing macrophage infiltration and M2 polarization, restricting TCR signaling, and inducing T cell apoptosis. A wide-variety of tumors also upregulate Gal-3, which is associated with poor prognosis. Tumor-bearing (MCA-205 sarcoma, 4T1 mammary carcinoma, TRAMP-C1 prostate adenocarcinoma) mice were treated with a Gal-3 inhibitor (belapectin; GR-MD-02), aOX40, or combination therapy and the extent of tumor growth was determined. The phenotype and function of tumor-infiltrating lymphocytes was determined by flow cytometry, multiplex cytokine assay, and multiplex immunohistochemistry. Gal-3 inhibition synergized with aOX40 to promote tumor regression and increase survival. Specifically, aOX40/belapectin therapy significantly improved survival of tumor-bearing mice through a CD8+ T cell-dependent mechanism. Combination aOX40/belapectin therapy enhanced CD8+ T cell density within the tumor and reduced the frequency and proliferation of regulatory Foxp3+CD4+ T cells. Further, aOX40/belapectin therapy significantly reduced monocytic MDSC (M-MDSCs) and MHC-IIhi macrophage populations, both of which displayed reduced arginase 1 and increased iNOS. Combination aOX40/belapectin therapy alleviated M-MDSC-specific functional suppression compared to M-MDSCs isolated from untreated tumors. Our data suggests that Gal-3 inhibition plus aOX40 therapy reduces M-MDSC-meditated immune suppression thereby increasing CD8+ T cell recruitment leading to increased tumor regression and survival.
Collapse
Affiliation(s)
- Elizabeth R Sturgill
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Annah S Rolig
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Stefanie N Linch
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Courtney Mick
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Melissa J Kasiewicz
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Zhaoyu Sun
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| | - Peter G Traber
- University of Pennsylvania School of Medicine, Philadelphia, PA, USA
| | | | - William L Redmond
- Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
| |
Collapse
|
|
27
|
Setayesh T, Colquhoun SD, Wan YJY. Overexpression of Galectin-1 and Galectin-3 in hepatocellular carcinoma. LIVER RESEARCH 2020; 4:173-179. [PMID: 34567824 PMCID: PMC8460053 DOI: 10.1016/j.livres.2020.11.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Galectins (Gals) are evolutionarily conserved proteins that bind to β-galactoside containing glycans. Abnormal expression of Gals is associated with the development, progression, and metastasis of different types of cancer. Among the 11 Gals identified in humans, the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors. Here, we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma (HCC). The overexpression of Gal-1 and Gal-3 correlates with tumor growth, HCC cell migration and invasion, tumor aggressiveness, metastasis, and poor prognosis. A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition. Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.
Collapse
Affiliation(s)
- Tahereh Setayesh
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA
| | | | - Yu-Jui Yvonne Wan
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA,Corresponding author. Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA. (Y.-J.Y. Wan)
| |
Collapse
|
|
28
|
Kong F, Jin M, Cao D, Jia Z, Liu Y, Jiang J. Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma. PeerJ 2020; 8:e9949. [PMID: 32995093 PMCID: PMC7501799 DOI: 10.7717/peerj.9949] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 08/25/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Galectins (Gal) are a family of protein that bind to the β-galactoside of glycoproteins. It modulates a variety of biological functions, such as tumor growth, angiogenesis and tumor metastasis. A series of experimental and clinical evidences have been reported to support a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to estimate the expression of Gal-3 and Gal-9 in order to evaluate their relation to hepatocellular carcinoma (HCC) -related clinical features and their prognostic values. METHODS We evaluated Gal-3 and Gal-9 expression in 247 HCC patients by a tissue microarray immunohistochemistry method, then analyzed the relationship between expression levels of Gal-3 and Gal-9 protein and tumor parameters or clinical outcomes. RESULTS The Gal-3 expression was significantly higher in tumor tissues compared with adjacent non-tumor tissues (P < 0.001), while no significant differences of Gal-9 was detected (P = 0.222). A higher Gal-3 expression was significantly associated with lymph-vascular invasion (P = 0.049), poor histological differentiation (P = 0.016), and no cirrhosis (P = 0.040). In contrast, a lower Gal-9 expression was related to lymph-vascular invasion (P = 0.012) and poor histological differentiation (P = 0.002). Survival analysis showed that patients with higher Gal-3 expression had worse overall survival (P = 0.012) , however no correlation was found between Gal-9 expression and survival (P = 0.185). Multivariate analysis showed that multiple tumor (HR = 1.94, 95% CI [1.36-2.78]), tumor size ≥ 5 cm (HR = 1.51, 95% CI [1.07-2.12]), Lymph-vascular invasion (HR = 1.45, 95% CI [1.00-2.10]) and Gal-3 expression (HR = 1.57, 95% CI [1.06-2.33]) were independent influencing factors of prognosis in patients with hepatocellular carcinoma. CONCLUSION Gal-3 was expected to serve as a novel prognostic marker of hepatocellular carcinoma, while Gal-9 expression was only related to tumor progression.
Collapse
Affiliation(s)
- Fei Kong
- Division of Clinical Research, the First Hospital of Jilin University, Changchun, China
- Department of Hepatology, the First Hospital of Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Meishan Jin
- Department of Pathology, the First Hospital of Jilin University, Changchun, China
| | - Donghui Cao
- Division of Clinical Research, the First Hospital of Jilin University, Changchun, China
| | - Zhifang Jia
- Division of Clinical Research, the First Hospital of Jilin University, Changchun, China
| | - Yawen Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Jing Jiang
- Division of Clinical Research, the First Hospital of Jilin University, Changchun, China
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| |
Collapse
|
|
29
|
Sun MJ, Cao ZQ, Leng P. The roles of galectins in hepatic diseases. J Mol Histol 2020; 51:473-484. [PMID: 32734557 DOI: 10.1007/s10735-020-09898-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 07/14/2020] [Indexed: 12/24/2022]
Abstract
Hepatic diseases include all diseases that occur in the liver, including hepatitis, cirrhosis, hepatocellular carcinoma, etc. Hepatic diseases worldwide are characterized by high incidences of digestive system diseases, which present with subtle symptoms, are difficult to treat and have high mortality. Galectins are β-galactoside-binding proteins that have been found to be aberrantly expressed during hepatic disease progression. An increasing number of studies have shown that abnormal expression of galectins is extensively involved in hepatic diseases, such as hepatocellular carcinoma (HCC), liver cirrhosis, hepatitis and liver fibrosis. Galectins function as intracellular and extracellular hepatic disease regulators mainly through the binding of their carbohydrate recognition domain to glycoconjugates expressed in hepatocytes. In this review, we summarize current research on the various roles of galectins in cirrhosis, hepatitis, liver fibrosis and HCC, which may provide a preliminary theoretical basis for the exploration of new targets for the treatment of hepatic diseases.
Collapse
Affiliation(s)
- Mei-Juan Sun
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, No. 16 Jiang Su Road, Qingdao, 266003, People's Republic of China
| | - Zhan-Qi Cao
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, No. 16 Jiang Su Road, Qingdao, 266003, People's Republic of China
| | - Ping Leng
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, No. 16 Jiang Su Road, Qingdao, 266003, People's Republic of China.
| |
Collapse
|
|
30
|
Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling. Br J Cancer 2020; 123:1145-1153. [PMID: 32624579 PMCID: PMC7525442 DOI: 10.1038/s41416-020-0971-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 06/01/2020] [Accepted: 06/17/2020] [Indexed: 12/24/2022] Open
Abstract
Background Wisteria floribunda agglutinin (WFA)+ Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC. Methods The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of M2BP were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated. Results M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC. Conclusions M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.
Collapse
|
|
31
|
A new risk model comprising genes highly correlated with CD133 identifies different tumor-immune microenvironment subtypes impacting prognosis in hepatocellular carcinoma. Aging (Albany NY) 2020; 12:12234-12250. [PMID: 32564007 PMCID: PMC7343494 DOI: 10.18632/aging.103409] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 05/25/2020] [Indexed: 12/13/2022]
Abstract
The existence of cancer stem cells (CSCs), marked by CD133, is the primary cause of death in hepatocellular carcinoma (HCC). Here, we generated a new risk model comprising the signatures of four genes highly correlated with CD133 (CD133(hi)) that help improve survival in HCC. Three datasets were used to identify the differential CD133(hi) genes by comparing sorted CD133+ liver CSCs and CD133- differentiated counterparts. Univariate analysis was used to screen significantly differential CD133(hi) genes associated with overall survival in the training dataset, which were used for risk model construction. High-risk patients were strongly associated with poor survival by Kaplan-Meier survival analysis in both the training and validation datasets. Clinical stratification analyses further demonstrated that the risk factors acted as independent factors and that high-risk patients were characterized by more aggressive cancer features. Functional enrichment analyses performed by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that high-risk patients showed the disturbance of immune hepatic homeostasis involving aberrant immune cells, including macrophages and T and B cells, and an abnormal inflammatory response including the IL6/Jak/STAT3 pathway and TNF signaling pathway. In conclusion, our constructed CD133(hi) gene risk model provides a resource for understanding the role of CD133+ CSCs in the progression of HCC in terms of tumor-immune interactions.
Collapse
|
|
32
|
Shao Q, He J, Chen Z, Wu C. Prognostic role of galectins expression in patients with hepatic cancer: A meta-analysis. Medicine (Baltimore) 2020; 99:e19622. [PMID: 32282710 PMCID: PMC7440300 DOI: 10.1097/md.0000000000019622] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 02/06/2020] [Accepted: 02/20/2020] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE The objective of this study was to illustrate the prognostic value of diversified galectins in patients with hepatic cancer via meta-analysis. METHODS We conducted a systematic search on PubMed, Embase, The Cochrane Library, Web of Science, the Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang Data for studies that reported associations between galectin expression and the prognosis for hepatic cancer patients, from the inception of each database to March 20, 2019. The combined hazard ratio (HR) and 95% confidence interval (CI) were estimated to investigate the prognosis. RESULTS We collected 11 studies of 1957 patients in our meta-analysis. The pooled results indicated that overall galectin expression was not correlated with OS (HR = 1.23, 95% CI = 0.84-1.79, P = .29) or DFS/RFS (HR = 0.808, 95% CI = 0.376-1.735, P = .42) in liver cancer patients. In stratified analyses, we observed that high galectin-1 and galectin-3 expression was significantly associated with poor OS. The pooled HR of galectin-4 and galectin-9 was correlated with improved OS. CONCLUSION Our results indicate that the high expression of galectin-1 and -3 and the low expression of galectin-4 and -9 may be predictive prognostic factors for poor OS in liver cancer patients.
Collapse
Affiliation(s)
- Qi Shao
- Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong
- The Third Affiliated Hospital of Soochow University, Changzhou
| | - Jing He
- Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong
| | - Zhiming Chen
- Department of Radiotherapy, Affiliated Hospital of Nantong University, Nantong
| | - Changping Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| |
Collapse
|
|
33
|
Ghapanchi J, Andisheh-Tadbir A, Torkaman P, Malekzadeh M, Mardani M. Evaluation of the serum levels of galectin-3 in patients with oral lichen planus disease. Oral Dis 2019; 25:466-470. [DOI: 10.1111/odi.13012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 10/31/2018] [Accepted: 11/20/2018] [Indexed: 11/29/2022]
Affiliation(s)
- Janan Ghapanchi
- Department of Oral and Maxillofacial Medicine, School of Dentistry; Shiraz University of Medical Sciences; Shiraz Iran
| | - Azadeh Andisheh-Tadbir
- Oral and Dental Disease Research Center, School of Dentistry; Shiraz University of Medical Sciences; Shiraz Iran
| | - Pooriya Torkaman
- Department of Oral and Maxillofacial Medicine, School of Dentistry; Shiraz University of Medical Sciences; Shiraz Iran
| | - Mahyar Malekzadeh
- Shiraz Institute for Cancer Research, School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
| | - Maryam Mardani
- Oral and Dental Disease Research Center, School of Dentistry; Shiraz University of Medical Sciences; Shiraz Iran
| |
Collapse
|
|
34
|
Wang Y, Liu S, Tian Y, Wang Y, Zhang Q, Zhou X, Meng X, Song N. Prognostic role of galectin-3 expression in patients with solid tumors: a meta-analysis of 36 eligible studies. Cancer Cell Int 2018; 18:172. [PMID: 30410421 PMCID: PMC6215616 DOI: 10.1186/s12935-018-0668-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 10/27/2018] [Indexed: 12/31/2022] Open
Abstract
Background Galectin-3 as a β-galactoside-binding protein, has been found to be involved in tumor cell growth, anti-apoptosis, adhesion, angiogenesis, invasion, and distant metastases, indicating that it may play a pivotal role in cancer development and progression. However, their results remain debatable and inconclusive. Hence, this meta-analysis was performed to clarify the precise predictive value of galectin-3 in various cancers. Methods PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wanfang databases were searched comprehensively for eligible studies up to July 15, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated to demonstrate their associations. Results A total of 36 relevant studies were ultimately enrolled in this meta-analysis. Our results shed light on the significant association of elevated galectin-3 expression with reduced OS or DFS/RFS/PFS in overall cancer patients (pooled HR = 1.79, 95% CI 1.42–2.27, I2= 67.3%, p < 0.01; pooled HR = 1.57, 95% CI 1.04–2.37, I2= 67.1%, p = 0.001). In tumor type subgroup analysis, we found high expression of galectin-3 was correlated with shorter OS or DFS/RFS/PFS in colorectal cancer (pooled HR = 3.05, 95% CI 2.13–4.35, I2= 0.0%, p = 0.734; pooled HR = 2.49, 95% CI 1.82–3.41, I2 = 0.0%, p = 0.738; respectively) and meanwhile it merely associated with reduced OS in ovarian cancer or non-small cell lung cancer (pooled HR = 2.24, 95% CI 1.38–3.64, I2= 0.0%, p = 0.910; pooled HR = 2.07, 95% CI 1.48–2.88, I2= 0.0%, p = 0.563; separately). Conclusions Taken together, our results suggested that galectin-3 played an oncogenic role in colorectal cancer, ovarian cancer and non-small cell lung cancer, indicating it could be a promising biomarker and a novel therapeutic target for them. Further studies were warranted to validate our findings.
Collapse
Affiliation(s)
- Yi Wang
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Shiwei Liu
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Ye Tian
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Yamin Wang
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Qijie Zhang
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Xiang Zhou
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Xianghu Meng
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| | - Ninghong Song
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029 Jiangsu China
| |
Collapse
|
|
35
|
Liu Y, Xie L, Wang D, Li D, Xu G, Wang L, Zhou H, Yu Y, Lin Z, Lu H. Galectin-3 and β-catenin are associated with a poor prognosis in serous epithelial ovarian cancer. Cancer Manag Res 2018; 10:3963-3971. [PMID: 30310317 PMCID: PMC6165784 DOI: 10.2147/cmar.s171146] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Purpose This study was designed to explore the expression levels of Galectin-3 (Gal-3) and β-catenin in serous epithelial ovarian cancer (SEOC), the linkage between their expressions, and the clinicopathological features of SEOC patients. Patients and methods Seventy-four SEOC patients' specimens were detected for Gal-3 and β-Catenin expressions using immunohistochemistry, and the association between β-catenin or Gal-3 protein expressions and clinicopathological features, treatment effects, and prognosis were analyzed using SPSS 19.0. Western blot was used to analyze protein expressions of Wnt/β-catenin pathway in ovarian cancer cell lines. Results There was a statistically significant positive correlation between Gal-3 and β-catenin expressions in SEOC (r=0.304 and P=0.001). Gal-3 expression was related to the grade (P=0.037), clinical stage (P=0.034), platinum resistance (P=0.030), and recurrence (P=0.001) in SEOC. There was a significant correlation between β-catenin with recurrence in SEOC (P=0.035). Platinum resistance (P=0.003) and Gal-3 expression (P<0.001) were independent risk factors for poorer overall survival (OS). OS of the strongly positive Gal-3 group was significantly lower than that of the negative and weakly positive groups (log-rank test, P=0.001). OS of the positive β-catenin group was lower than that of the negative β-catenin group (log-rank test, P=0.034). Downregulating Gal-3 expression attenuated the protein expressions of Wnt/β-catenin pathway in ovarian cancer cell lines. Conclusion Gal-3 might activate Wnt/β-catenin signaling pathway in SEOC. Hence, Gal-3 may serve as a prognostic factor for SEOC. Targeting Gal-3 may be a promising new treatment approach for SEOC.
Collapse
Affiliation(s)
- Yunyun Liu
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China, .,Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Lingling Xie
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China, .,Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Dongyan Wang
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Da Li
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Guocai Xu
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Lijuan Wang
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Hui Zhou
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Yuefei Yu
- Department of Research and Development, Guangzhou Hengtai Biotech Ltd, Guangzhou, Guangdong, China.,Department of Research and Development, Ameritech Biomedicines, Inc., Houston, TX, USA
| | - Zhongqiu Lin
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China,
| | - Huaiwu Lu
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China, .,Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, Guangdong, China,
| |
Collapse
|
|
36
|
Dubé-Delarosbil C, St-Pierre Y. The emerging role of galectins in high-fatality cancers. Cell Mol Life Sci 2018; 75:1215-1226. [PMID: 29119229 PMCID: PMC11105754 DOI: 10.1007/s00018-017-2708-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 10/16/2017] [Accepted: 11/02/2017] [Indexed: 12/13/2022]
Abstract
Although we witnessed considerable progress in the prevention and treatment of cancer during the past few decades, a number of cancers remain difficult to treat. The main reasons for this are a lack of effective biomarkers necessary for an early detection and inefficient treatments for cancer that are diagnosed at late stages of the disease. Because of their alarmin-like properties and their protumorigenic role during cancer progression, members of the galectin family are uniquely positioned to provide information that could be used for the exploration of possible avenues for the treatment of high fatality cancer (HFC). A rapid overview of studies that examined the expressions and functions of galectins in cancer cells reveals that they play a central role in at least three major features that characterize HFCs: (1) induction of systemic and local immunosuppression, (2) chemoresistance of cancer cells, and (3) increased invasive behavior. Defining the galectinome in HFCs will also lead to a better understanding of tumor heterogeneity while providing critical information that could improve the accuracy of biomarker panels for a more personalized treatment of HFCs. In this review, we discuss the relevance of the galectinome in HFC and its possible contribution to providing potential solutions.
Collapse
Affiliation(s)
| | - Yves St-Pierre
- INRS-Institut Armand-Frappier, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada.
| |
Collapse
|
|
37
|
Ajani JA, Estrella JS, Chen Q, Correa AM, Ma L, Scott AW, Jin J, Liu B, Xie M, Sudo K, Shiozaki H, Badgwell B, Weston B, Lee JH, Bhutani MS, Onodera H, Suzuki K, Suzuki A, Ding S, Hofstetter WL, Johnson RL, Bresalier RS, Song S. Galectin-3 expression is prognostic in diffuse type gastric adenocarcinoma, confers aggressive phenotype, and can be targeted by YAP1/BET inhibitors. Br J Cancer 2018; 118:52-61. [PMID: 29136404 PMCID: PMC5765229 DOI: 10.1038/bjc.2017.388] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/24/2017] [Accepted: 10/04/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Overexpression of Galectin-3 (Gal-3), a β-galactoside binding protein, has been noted in many tumour types but its functional significance and clinical utility in gastric adenocarcinoma (GAC) are not well known. METHODS We studied 184 GAC patients characterised by histologic grade, sub-phenotypes (diffuse vs intestinal), and ethnicity (Asians vs North Americans). Immunohistochemistry was performed to assess the expression of Gal-3 in human GACs and we correlated it to the clinical outcomes. Cell proliferation, invasion, co-immunoprecipitation and kinase activity assays were done in genetically stable Gal-3 overexpressing GC cell lines and the parental counterparts to delineate the mechanisms of action and activity of inhibitors. RESULTS Most patients were men, Asian, and had a poorly differentiated GAC. Gal-3 was over-expressed in poorly differentiated (P=0.002) tumours and also in diffuse sub-phenotype (P=0.02). Gal-3 overexpression was associated with shorter overall survival (OS; P=0.026) in all patients. Although, Gal-3 over-expression was not prognostic in the Asian cohort (P=0.337), it was highly prognostic in the North American cohort (P=0.001). In a multivariate analysis, Gal-3 (P=0.001) and N-stage (P=<0.001) were independently prognostic for shorter OS. Mechanistically, Gal-3 induced c-MYC expression through increasing RalA activity and an enhanced YAP1/RalA/RalBP complex to confer an aggressive phenotype. YAP1/BET bromodomain inhibitors reduced Gal-3-mediated aggressive phenotypes in GAC cells. CONCLUSIONS Gal-3 is an independent prognostic marker of shorter OS and a novel therapeutic target particularly in diffuse type GAC in North American patients.
Collapse
Affiliation(s)
- Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Jeannelyn S Estrella
- Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Qiongrong Chen
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Arlene M Correa
- Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Lang Ma
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Ailing W Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Bin Liu
- Department of Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Min Xie
- Department of Pharmaceuical Chemistry, University of California-San Francisco, San Francisco, CA 94158, USA
| | - Kazuki Sudo
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Hironori Shiozaki
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian Badgwell
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian Weston
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Manoop S Bhutani
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Hisashi Onodera
- Education Center, St. Luke's International University, Tokyo 104-8560, Japan
| | - Koyu Suzuki
- Department of Pathology, St. Luke's International Hospital, Tokyo 104-8560, Japan
| | - Akihiro Suzuki
- Department of Gastrointestinal Surgery, St. Luke's International Hospital, Tokyo 104-8560, Japan
| | - Sheng Ding
- Department of Pharmaceuical Chemistry, University of California-San Francisco, San Francisco, CA 94158, USA
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Randy L Johnson
- Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Robert S Bresalier
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| |
Collapse
|
|
38
|
Dong R, Zhang M, Hu Q, Zheng S, Soh A, Zheng Y, Yuan H. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). Int J Mol Med 2017; 41:599-614. [PMID: 29207027 PMCID: PMC5752178 DOI: 10.3892/ijmm.2017.3311] [Citation(s) in RCA: 173] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 11/29/2017] [Indexed: 01/03/2023] Open
Abstract
Galectin-3 is a member of the galectin family, which are β‑galactoside‑binding lectins with ≥1 evolutionary conserved carbohydrate‑recognition domain. It binds proteins in a carbohydrate‑dependent and ‑independent manner. Galectin‑3 is predominantly located in the cytoplasm; however, it shuttles into the nucleus and is secreted onto the cell surface and into biological fluids including serum and urine. It serves important functions in numerous biological activities including cell growth, apoptosis, pre‑mRNA splicing, differentiation, transformation, angiogenesis, inflammation, fibrosis and host defense. Numerous previous studies have indicated that galectin‑3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer. With emerging evidence to support the function and application of galectin‑3, the current review aims to summarize the latest literature regarding the biomarker characteristics and potential therapeutic application of galectin‑3 in associated diseases.
Collapse
Affiliation(s)
- Rui Dong
- Department of Pediatric Hepatobiliary Surgery, Children's Hospital of Fudan University and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 200433, P.R. China
| | - Min Zhang
- Medical College, Xizang Minzu University, Xianyang, Shaanxi 712000, P.R. China
| | - Qunying Hu
- Medical College, Xizang Minzu University, Xianyang, Shaanxi 712000, P.R. China
| | - Shan Zheng
- Department of Pediatric Hepatobiliary Surgery, Children's Hospital of Fudan University and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 200433, P.R. China
| | - Andrew Soh
- Medical Scientific Affairs, Abbott Diagnostics Division, Abbott Laboratories, Shanghai 200032, P.R. China
| | - Yijie Zheng
- Medical Scientific Affairs, Abbott Diagnostics Division, Abbott Laboratories, Shanghai 200032, P.R. China
| | - Hui Yuan
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
| |
Collapse
|
|
39
|
Arbelaiz A, Azkargorta M, Krawczyk M, Santos-Laso A, Lapitz A, Perugorria MJ, Erice O, Gonzalez E, Jimenez-Agüero R, Lacasta A, Ibarra C, Sanchez-Campos A, Jimeno JP, Lammert F, Milkiewicz P, Marzioni M, Macias RIR, Marin JJG, Patel T, Gores GJ, Martinez I, Elortza F, Falcon-Perez JM, Bujanda L, Banales JM. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2017; 66:1125-1143. [PMID: 28555885 DOI: 10.1002/hep.29291] [Citation(s) in RCA: 219] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 04/29/2017] [Accepted: 05/24/2017] [Indexed: 02/06/2023]
Abstract
UNLABELLED Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions, such as primary sclerosing cholangitis (PSC), are risk factors. Noninvasive differential diagnosis between intrahepatic CCA and hepatocellular carcinoma (HCC) is sometimes difficult. Accurate noninvasive biomarkers for PSC, CCA, and HCC are not available. In the search for novel biomarkers, serum extracellular vesicles (EV) were isolated from CCA (n = 43), PSC (n = 30), or HCC (n = 29) patients and healthy individuals (control, n = 32); and their protein content was characterized. By using nanoparticle tracking analysis, serum EV concentration was found to be higher in HCC than in all the other groups. Round morphology (by transmission electron microscopy), size (∼180 nm diameter by nanoparticle tracking analysis), and markers (clusters of differentiation 9, 63, and 81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed multiple differentially expressed proteins among groups. Several of these proteins showed high diagnostic values with maximum area under the receiver operating characteristic curve of 0.878 for CCA versus control, 0.905 for CCA stage I-II versus control, 0.789 for PSC versus control, 0.806 for noncirhottic PSC versus control, 0.796 for CCA versus PSC, 0.956 for CCA stage I-II versus PSC, 0.904 for HCC versus control, and 0.894 for intrahepatic CCA versus HCC. Proteomic analysis of EV derived from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by normal human cholangiocytes. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release to serum of EV containing some similar human oncogenic proteins. CONCLUSION Proteomic signatures found in serum EV of CCA, PSC, and HCC patients show potential usefulness as diagnostic tools. (Hepatology 2017;66:1125-1143).
Collapse
Affiliation(s)
- Ander Arbelaiz
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Mikel Azkargorta
- Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Alvaro Santos-Laso
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Ainhoa Lapitz
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Oihane Erice
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | | | - Raul Jimenez-Agüero
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Adelaida Lacasta
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | | | | | | | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Marco Marzioni
- Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy
| | - Rocio I R Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
| | - Jose J G Marin
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
| | - Tushar Patel
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Félix Elortza
- Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Juan M Falcon-Perez
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Metabolomics Unit, CIC bioGUNE, CIBERehd, Derio, Spain
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| |
Collapse
|
|
40
|
Chen C, Wang G, Huang X, Dong X, Chen G, Lin M, Cai Z, Zeng Y. Overexpression of galectin-4 promotes cell growth of hepatocellular carcinoma cells in vitro and in vivo. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:10233-10242. [PMID: 31966357 PMCID: PMC6965780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 08/09/2017] [Indexed: 06/10/2023]
Abstract
Galectin-4 is a member of multifunctional galactoside-binding lectin family with various biological functions, including tumor cells proliferation, cancer progression, cell adhesion, and tumor metastasis. In this study, we aimed to investigate the putative function of galectin-4 in tumor progression of hepatocellular carcinoma (HCC), and explore the possible mechanisms of galectin-4 related biological pathway. The result showed that the galectin-4 was significantly up-regulated in HCC tissues/cell lines compared to matched peritumor tissues/a normal liver cell line, respectively. Furthermore, overexpressing galectin-4 in HCCLM3 cells led to promotion of cell proliferation and inhibition of cell apoptosis via up-regulation of Cyclin D1, down-regulation of p21 and decreased pro-apoptotic Bax/Bcl-2 ratio, But knockdown of galectin-4 reversed these properties. Furthermore, galectin-4 could promote cell-cell adhesion via stabilizing the adherens junction complexes. These observations was further validated in the xenograft animal model. Taken together, galectin-4 plays an important role in HCC progression.
Collapse
Affiliation(s)
- Cancan Chen
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical UniversityFuzhou, China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Gaoxiong Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou, China
| | - Xinhui Huang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Xiuqing Dong
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Geng Chen
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Mingjie Lin
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Zhixiong Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| | - Yongyi Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical UniversityFuzhou, China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou, China
| |
Collapse
|
|
41
|
Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma. Sci Rep 2017; 7:5189. [PMID: 28701735 PMCID: PMC5507876 DOI: 10.1038/s41598-017-05419-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Accepted: 05/30/2017] [Indexed: 01/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a serious threat to human health. The carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC and its possible molecular mechanism with quantitative proteomics approach. We found that rGal3C stimulation could inhibit cell viability, migration and invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially expressed. Eighty up-regulated proteins located mainly in extracellular exosome and involved in cell adhesion and metabolism, and 110 down-regulated proteins located in mitochondria and extracellular exosome, and related to processes of metabolism and oxidation-reduction. Of the differentially expressed proteins, CLU, NDRG1, CD166, S100A11 and Galectin-1 were carcinoma-related proteins affected by rGal3C. Potential receptors of rGal3C were explored by an UV cross-linking capture strategy. We showed that rGal3C could induce dephosphorylating of FAK/SRC. Blocking of the FAK/SRC pathway resulted in down-regulation of NDRG1. Immunofluorescence suggested that rGal3C could disrupt integrin clustering. Our study provides valuable insight into the anti-tumour mechanism of rGal3C in HCC on a proteomics level and is the first to reveal the possible mechanism involving integrin/FAK/SRC pathway and NDRG1. These results provide useful guidance of developing new therapies for HCC.
Collapse
|
|
42
|
Shimura T, Kofunato Y, Okada R, Yashima R, Koyama Y, Araki K, Kuwano H, Takenoshita S. Intranuclear accumulation of galectin-3 is an independent prognostic factor for patients with distal cholangiocarcinoma. Oncol Lett 2017; 14:819-829. [PMID: 28693238 PMCID: PMC5494714 DOI: 10.3892/ol.2017.6252] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 03/09/2017] [Indexed: 12/26/2022] Open
Abstract
Galectin-3 has been reported to be associated with the prognosis of patients with various malignancies; however, it has not yet been investigated in patients with extrahepatic cholangiocarcinoma (EHCC). Expression of galectin-3 was retrospectively examined in 58 patients with EHCC: 21 with perihilar cholangiocarcinoma and 37 with distal cholangiocarcinoma (DCC). The Cox proportional hazard model was used to identify independent prognostic factors. Intranuclear accumulation of galectin-3 (gal-3-INA) was associated with poorer overall survival (OS) in all patients (P=0.003), as well as in patients with DCC (P=0.004). Patients with gal-3-INA also exhibited a poorer disease-free survival (DFS) than those without gal-3-INA in all patients with EHCC (P<0.001), and in patients with DCC (P<0.001). Gal-3-INA was an independent prognostic factor of OS and DFS in all patients [OS: Hazard ratio (HR), 4.470; 95% confidence interval (CI), 1.759–11.357; P=0.002; and DFS: HR, 5.116; 95% CI, 2.025–12.925; P=0.001]. Gal-3-INA was also an independent prognostic factor in patients with DCC (OS: HR, 2.979; 95% CI, 1.035–8.570; P=0.043; and DFS: HR, 6.773; 95% CI, 1.558–29.439; P=0.011). In the analysis of patients with DCC, the number of patients with high galectin-3 expression (P=0.038), recurrence (P<0.001), distant metastases (P<0.001), R0 status (P=0.029) or microscopic vascular invasion (P=0.019) was significantly higher in the gal-3-INA-positive group than in the gal-3-INA-negative group. In conclusion, gal-3-INA was identified as a strong prognostic factor for OS and DFS in patients with DCC.
Collapse
Affiliation(s)
- Tatsuo Shimura
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Yasuhide Kofunato
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Ryo Okada
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Rei Yashima
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Yoshihisa Koyama
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Kenichiro Araki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
| | - Seiichi Takenoshita
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| |
Collapse
|
|
43
|
Tummala KS, Brandt M, Teijeiro A, Graña O, Schwabe RF, Perna C, Djouder N. Hepatocellular Carcinomas Originate Predominantly from Hepatocytes and Benign Lesions from Hepatic Progenitor Cells. Cell Rep 2017; 19:584-600. [PMID: 28423321 PMCID: PMC5409928 DOI: 10.1016/j.celrep.2017.03.059] [Citation(s) in RCA: 102] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 02/08/2017] [Accepted: 03/21/2017] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However, its origin remains a debated question. Using human data and various hepatocarcinogenesis mouse models, we show that, in early stages, transformed hepatocytes, independent of their proliferation status, activate hepatic progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes reveals that, in all models, HCC originates from hepatocytes. However, whereas in various models tumors do not emanate from HPCs, tracking of progenitors in a model mimicking human hepatocarcinogenesis indicates that HPCs can generate benign lesions (regenerative nodules and adenomas) and aggressive HCCs. Mechanistically, galectin-3 and α-ketoglutarate paracrine signals emanating from oncogene-expressing hepatocytes instruct HPCs toward HCCs. α-Ketoglutarate preserves an HPC undifferentiated state, and galectin-3 maintains HPC stemness, expansion, and aggressiveness. Pharmacological or genetic blockage of galectin-3 reduces HCC, and its expression in human HCC correlates with poor survival. Our findings may have clinical implications for liver regeneration and HCC therapy.
Collapse
Affiliation(s)
- Krishna S Tummala
- Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Marta Brandt
- Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Ana Teijeiro
- Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Osvaldo Graña
- Structural Biology and Biocomputing Programme, Bioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Robert F Schwabe
- Department of Medicine, Columbia University, New York, NY 10032, USA
| | - Cristian Perna
- Department of Pathology, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid 28034, Spain
| | - Nabil Djouder
- Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain.
| |
Collapse
|
|
44
|
The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial-Mesenchymal Transition. Int J Mol Sci 2017; 18:ijms18030500. [PMID: 28264434 PMCID: PMC5372516 DOI: 10.3390/ijms18030500] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 02/20/2017] [Accepted: 02/21/2017] [Indexed: 12/27/2022] Open
Abstract
The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT) in many tumors. Vasculogenic mimicry (VM) is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC). We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation of Runx2 in HepG2 cells, and increased in SMMC7721 cells after Runx2 knockdown. We consistently demonstrated that the downregulation of LGALS3 in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation of LGALS3 in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process.
Collapse
|
|
45
|
Gao N, Wang XX, Sun JR, Yu WZ, Li XZ. Clinical impact of galectin-3 in newly diagnosed t (15;17)(q22;q21)/PML-RARa acute promyelocytic leukemia treated with all-trans retinoic acid and arsenic trioxide-based regimens. Ann Hematol 2017; 96:711-718. [DOI: 10.1007/s00277-017-2948-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 02/04/2017] [Indexed: 11/30/2022]
|
|
46
|
Al-Maghrabi J, Abdelrahman AS, Ghabrah T, Butt NS, Al-Maghrabi B, Khabaz MN. Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas. Pathol Res Pract 2017; 213:348-352. [PMID: 28215640 DOI: 10.1016/j.prp.2017.01.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 01/15/2017] [Accepted: 01/15/2017] [Indexed: 01/16/2023]
Abstract
This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients.
Collapse
Affiliation(s)
- Jaudah Al-Maghrabi
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Amer Shafie Abdelrahman
- Department of Pathology, Rabigh Faculty of Medicine, King Abdulaziz University, P.O. Box: 80205, Jeddah 21589, Saudi Arabia
| | - Tawfik Ghabrah
- Department of Family and Community Medicine, Rabigh Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nadeem Shafique Butt
- Department of Family and Community Medicine, Rabigh Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Basim Al-Maghrabi
- Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohamad Nidal Khabaz
- Department of Pathology, Rabigh Faculty of Medicine, King Abdulaziz University, P.O. Box: 80205, Jeddah 21589, Saudi Arabia.
| |
Collapse
|
|
47
|
Norton P, Comunale MA, Herrera H, Wang M, Houser J, Wimmerova M, Romano PR, Mehta A. Development and application of a novel recombinant Aleuria aurantia lectin with enhanced core fucose binding for identification of glycoprotein biomarkers of hepatocellular carcinoma. Proteomics 2016; 16:3126-3136. [PMID: 27650323 DOI: 10.1002/pmic.201600064] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 06/27/2016] [Accepted: 09/16/2016] [Indexed: 01/01/2023]
Abstract
The Aleuria aurantia lectin (AAL) derived from orange peel fungus contains five fucose-binding sites that recognizes fucose bound in α-1,2, α-1,3, α-1,4, and α-1,6 linkages to N-acetylglucosamine and galactose. Recently, we have created several recombinant AAL (rAAL) proteins that had altered binding affinity to fucose linkages. In this report, we further characterize the binding specificity of one of the mutated lectins, N224Q lectin. This lectin was characterized by lectin Western blotting, surface plasmon resonance, and glycan microarray and shown to have increased binding to fucosylated glycan. Subsequently, we used this lectin to identify secreted fucosylated glycoproteins from a fetal hepatic cell line. Proteomic analysis revealed several glycoproteins secreted by the fetal cell line that were bound by N224Q lectin. These findings were confirmed by subsequent proteomic analysis of human serum from control patients or patients with hepatocellular carcinoma. These represent candidate oncofetal markers for liver cancer.
Collapse
Affiliation(s)
- Pamela Norton
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Mary Ann Comunale
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Harmin Herrera
- Graduate School of Biomedical Sciences and Professional Studies, Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Mengjun Wang
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Josef Houser
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Michaela Wimmerova
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | | | - Anand Mehta
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA
| |
Collapse
|
|
48
|
Gao N, Yu WZ, Guo NJ, Wang XX, Sun JR. Clinical significance of galectin-3 in patients with adult acute myeloid leukemia: a retrospective cohort study with long-term follow-up and formulation of risk scoring system. Leuk Lymphoma 2016; 58:1394-1402. [PMID: 27736291 DOI: 10.1080/10428194.2016.1243677] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Galectin-3 plays an increasingly important role in development and progression of tumor. However, little is known about the clinical impact of galectin-3 in non-acute promyelocytic leukemia (non-M3 AML). Peripheral blood of 298 patients with primary non-M3 AML and 30 normal donors was collected for measurement of galectin-3. Galectin-3 levels were significantly higher compared with the control group (p < .001). Patients with higher galectin-3 levels had lower CR rates (p = .001) and 1-year overall survival (OS) rates (p = .002). The Kaplan-Meier survival analysis showed that higher galectin-3 levels group had significantly shorter OS. Cox regression model revealed high galectin-3 level was an independent poor prognostic factor. A scoring system incorporating galectin-3 and other prognostic factors (age, WBC, karyotype, NPM1/FLT3-ITD, CEBPAdouble-mutation and c-KIT, WT1) was formulated to predict prognosis. In conclusion, galectin-3 may be a reliable prognostic marker in AML patients. The multifactorial scoring system was more powerful than a single factor to predict clinical outcome.
Collapse
Affiliation(s)
- Na Gao
- a Department of hematology , Binzhou Medical University Hospital , Binzhou , Shandong , PR China
| | - Wen-Zheng Yu
- a Department of hematology , Binzhou Medical University Hospital , Binzhou , Shandong , PR China
| | - Nong-Jian Guo
- b Department of hematology, Central Hospital of Jinan , Shandong University School of Medicine , Jinan , Shandong , PR China
| | - Xue-Xia Wang
- a Department of hematology , Binzhou Medical University Hospital , Binzhou , Shandong , PR China
| | - Jian-Rong Sun
- a Department of hematology , Binzhou Medical University Hospital , Binzhou , Shandong , PR China
| |
Collapse
|
|
49
|
Manzi M, Bacigalupo ML, Carabias P, Elola MT, Wolfenstein-Todel C, Rabinovich GA, Espelt MV, Troncoso MF. Galectin-1 Controls the Proliferation and Migration of Liver Sinusoidal Endothelial Cells and Their Interaction With Hepatocarcinoma Cells. J Cell Physiol 2016; 231:1522-1533. [PMID: 26551914 DOI: 10.1002/jcp.25244] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 10/22/2015] [Indexed: 01/05/2023]
Abstract
Galectin-1 (Gal1), a β-galactoside-binding protein elevated in hepatocellular carcinoma (HCC), promotes epithelial-mesenchymal transition (EMT) and its expression correlates with HCC growth, invasiveness, and metastasis. During the early stages of HCC, transforming growth factor β1 (TGF-β1 ) acts as a tumor suppressor; however in advanced stages, HCC cells lose their cytostatic response to TGF-β1 and undergo EMT. Here, we investigated the role of Gal1 on liver endothelial cell biology, and the interplay between Gal1 and TGF-β1 in HCC progression. By Western blot and immunofluorescence, we analyzed Gal1 expression, secretion and localization in HepG2 and HuH-7 human HCC cells, and in SK-HEP-1 human liver sinusoidal endothelial cells (SECs). We used loss-of-function and gain-of-function experiments to down- or up-regulate Gal1 expression, respectively, in HepG2 cells. We cultured SK-HEP-1 cells with conditioned media from HCC cells secreting different levels of Gal1, and demonstrated that Gal1 derived from tumor hepatocytes induced its own expression in SECs. Colorimetric and scratch-wound assays revealed that secretion of Gal1 by HCC cells induced SEC proliferation and migration. Moreover, by fluorescence microscopy we demonstrated that Gal1 promoted glycan-dependent heterotypic adhesion of HepG2 cells to SK-HEP-1 SECs. Furthermore, TGF-β1 induced Gal1 expression and secretion by HCC cells, and promoted HepG2 cell adhesion to SK-HEP-1 SECs through a Gal1-dependent mechanism. Finally, Gal1 modulated HepG2 cell proliferation and sensitivity to TGF-β1 -induced growth inhibition. Our results suggest that Gal1 and TGF-β1 might function coordinately within the HCC microenvironment to regulate tumor growth, invasion, metastasis, and angiogenesis.
Collapse
Affiliation(s)
- Malena Manzi
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - María L Bacigalupo
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - Pablo Carabias
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - María T Elola
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - Carlota Wolfenstein-Todel
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - Gabriel A Rabinovich
- Institute of Biology and Experimental Medicine (CONICET) and School of Exact and Natural Sciences, University of Buenos Aires (UBA), Buenos Aires, Argentina
| | - María V Espelt
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| | - María F Troncoso
- Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Institute of Biological Chemistry and Biophysics "Prof. Alejandro C. Paladini", University of Buenos Aires (UBA)-National Research Council of Argentina (CONICET), Buenos Aires, Argentina
| |
Collapse
|
|
50
|
Li G, Gao Y, Cui L, Wu L, Yang X, Chen J. Anguilla japonicalectin 1 delivery through adenovirus vector induces apoptotic cancer cell death through interaction with PRMT5. J Gene Med 2016; 18:65-74. [DOI: 10.1002/jgm.2878] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 02/20/2016] [Accepted: 03/07/2016] [Indexed: 12/22/2022] Open
Affiliation(s)
- Gongchu Li
- College of Life Sciences; Zhejiang Sci-Tech University; Hangzhou Zhejiang China
| | - Yajun Gao
- College of Life Sciences; Zhejiang Sci-Tech University; Hangzhou Zhejiang China
| | - Lianzhen Cui
- College of Life Sciences; Zhejiang Sci-Tech University; Hangzhou Zhejiang China
| | - Liqin Wu
- College of Life Sciences; Zhejiang Sci-Tech University; Hangzhou Zhejiang China
| | - Xinyan Yang
- College of Life Sciences; Zhejiang Sci-Tech University; Hangzhou Zhejiang China
| | - Jing Chen
- Institute of Life Sciences, College of Life and Environmental Sciences; Hangzhou Normal University; Hangzhou Zhejiang China
| |
Collapse
|