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Qian WJ, Yan JS, Gang XY, Xu L, Shi S, Li X, Na FJ, Cai LT, Li HM, Zhao MF. Intercellular adhesion molecule-1 (ICAM-1): From molecular functions to clinical applications in cancer investigation. Biochim Biophys Acta Rev Cancer 2024; 1879:189187. [PMID: 39317271 DOI: 10.1016/j.bbcan.2024.189187] [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: 03/18/2024] [Revised: 09/17/2024] [Accepted: 09/19/2024] [Indexed: 09/26/2024]
Abstract
Intercellular adhesion molecule-1 (ICAM-1) is a versatile molecule that plays a critical role in various physiological and pathological processes, particularly in tumor development where its impact is bidirectional. On the one hand, it augments the immune response by promoting immune cell migration, infiltration, and the formation of immunological synapses, thus facilitating potent antitumor effects. Simultaneously, it contributes to tumor immune evasion and influences metastasis by mediating transendothelial migration (TEM), epithelial-to-mesenchymal transition (EMT), and epigenetic modification of tumor cells. Despite its significant potential, the full clinical utility of ICAM-1 has yet to be fully realized. In this review, we thoroughly examine recent advancements in understanding the role of ICAM-1 in tumor development, its relevance in predicting therapeutic efficacy and prognosis, as well as the progress in clinical translational research on anti-ICAM-1-based therapies, encompassing including monoclonal antibodies, immunotherapy, antibody-drug conjugate (ADC), and conventional treatments. By shedding light on these innovative strategies, we aim to underscore ICAM-1's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
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Affiliation(s)
- Wen-Jing Qian
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jin-Shan Yan
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Xiao-Yu Gang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Lu Xu
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Sha Shi
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Xin Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Fang-Jian Na
- Network Information Center, China Medical University, Shenyang, China
| | - Lu-Tong Cai
- Psychological Medicine, Shenyang Medical College, Shenyang, China
| | - He-Ming Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China; Guangdong Association of Clinical Trials (GACT)/Chinese Thoracic Oncology Group (CTONG) and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer, Guangzhou, China.
| | - Ming-Fang Zhao
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China.
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Mastrogiovanni M, Donnadieu E, Pathak R, Di Bartolo V. Subverting Attachment to Prevent Attacking: Alteration of Effector Immune Cell Migration and Adhesion as a Key Mechanism of Tumor Immune Evasion. BIOLOGY 2024; 13:860. [PMID: 39596815 PMCID: PMC11591779 DOI: 10.3390/biology13110860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/19/2024] [Accepted: 10/22/2024] [Indexed: 11/29/2024]
Abstract
Cell adhesion regulates specific migratory patterns, location, communication with other cells, physical interactions with the extracellular matrix, and the establishment of effector programs. Proper immune control of cancer strongly depends on all these events occurring in a highly accurate spatiotemporal sequence. In response to cancer-associated inflammatory signals, effector immune cells navigating the bloodstream shift from their patrolling exploratory migration mode to establish adhesive interactions with vascular endothelial cells. This interaction enables them to extravasate through the blood vessel walls and access the cancer site. Further adhesive interactions within the tumor microenvironment (TME) are crucial for coordinating their distribution in situ and for mounting an effective anti-tumor immune response. In this review, we examine how alterations of adhesion cues in the tumor context favor tumor escape by affecting effector immune cell infiltration and trafficking within the TME. We discuss the mechanisms by which tumors directly modulate immune cell adhesion and migration patterns to affect anti-tumor immunity and favor tumor evasion. We also explore indirect immune escape mechanisms that involve modifications of TME characteristics, such as vascularization, immunogenicity, and structural topography. Finally, we highlight the significance of these aspects in designing more effective drug treatments and cellular immunotherapies.
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Affiliation(s)
- Marta Mastrogiovanni
- Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Emmanuel Donnadieu
- Equipe Labellisée Ligue Contre le Cancer, CNRS, INSERM, Institut Cochin, Université Paris Cité, F-75014 Paris, France;
| | - Rajiv Pathak
- Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA;
| | - Vincenzo Di Bartolo
- Immunoregulation Unit, Institut Pasteur, Université Paris Cité, F-75015 Paris, France;
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Sulit AK, Kolisnik T, Frizelle FA, Purcell R, Schmeier S. MetaFunc: taxonomic and functional analyses of high throughput sequencing for microbiomes. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2023; 4:e4. [PMID: 39295912 PMCID: PMC11406379 DOI: 10.1017/gmb.2022.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/06/2022] [Accepted: 12/13/2022] [Indexed: 09/21/2024]
Abstract
The identification of functional processes taking place in microbiome communities augment traditional microbiome taxonomic studies, giving a more complete picture of interactions taking place within the community. While there are applications that perform functional annotation on metagenomes or metatranscriptomes, very few of these are able to link taxonomic identity to function or are limited by their input types or databases used. Here we present MetaFunc, a workflow which takes RNA sequences as input reads, and from these (1) identifies species present in the microbiome sample and (2) provides gene ontology annotations associated with the species identified. In addition, MetaFunc allows for host gene analysis, mapping the reads to a host genome, and separating these reads, prior to microbiome analyses. Differential abundance analysis for microbe taxonomies, and differential gene expression analysis and gene set enrichment analysis may then be carried out through the pipeline. A final correlation analysis between microbial species and host genes can also be performed. Finally, MetaFunc builds an R shiny application that allows users to view and interact with the microbiome results. In this paper, we showed how MetaFunc can be applied to metatranscriptomic datasets of colorectal cancer.
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Affiliation(s)
- Arielle Kae Sulit
- Department of Surgery, University of Otago, Christchurch, New Zealand
- School of Natural Sciences, Massey University, Auckland, New Zealand
| | - Tyler Kolisnik
- School of Natural Sciences, Massey University, Auckland, New Zealand
| | | | - Rachel Purcell
- Department of Surgery, University of Otago, Christchurch, New Zealand
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Qiu Z, Wang Y, Zhang Z, Qin R, Peng Y, Tang W, Xi Y, Tian G, Zhang Y. Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications. Front Oncol 2022; 12:1052672. [PMID: 36505809 PMCID: PMC9728583 DOI: 10.3389/fonc.2022.1052672] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 11/09/2022] [Indexed: 11/24/2022] Open
Abstract
Colorectal cancer (CRC) is a major global health problem and one of the major causes of cancer-related death worldwide. It is very important to understand the pathogenesis of CRC for early diagnosis, prevention strategies and identification of new therapeutic targets. Intercellular adhesion molecule-1 (ICAM-1, CD54) displays an important role in the the pathogenesis of CRC. It is a cell surface glycoprotein of the immunoglobulin (Ig) superfamily and plays an essential role in cell-cell, cell-extracellular matrix interaction, cell signaling and immune process. It is also expressed by tumor cells and modulates their functions, including apoptosis, cell motility, invasion and angiogenesis. The interaction between ICAM-1 and its ligand may facilitate adhesion of tumor cells to the vascular endothelium and subsequently in the promotion of metastasis. ICAM-1 expression determines malignant potential of cancer. In this review, we will discuss the expression, function, prognosis, tumorigenesis, polymorphisms and therapeutic implications of ICAM-1 in CRC.
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Affiliation(s)
- Zhiyuan Qiu
- Department of Oncology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yan Wang
- Department of Oncology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhao Zhang
- Department of Oncology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Rong Qin
- Department of Oncology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yong Peng
- Department of Oncology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Weifeng Tang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China
| | - Yan Xi
- Department of Geriatrics, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Guangyu Tian
- Department of Oncology, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, China
| | - Yeqing Zhang
- Department of Vascular Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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Bronikowska J, Kłósek M, Janeczko T, Kostrzewa-Susłow E, Czuba ZP. The modulating effect of methoxy-derivatives of 2'-hydroxychalcones on the release of IL-8, MIF, VCAM-1 and ICAM-1 by colon cancer cells. Biomed Pharmacother 2021; 145:112428. [PMID: 34800781 DOI: 10.1016/j.biopha.2021.112428] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 11/09/2021] [Accepted: 11/12/2021] [Indexed: 12/15/2022] Open
Abstract
Colon cancer is one of the leading causes of death in the world. The search for effective and minimally invasive methods of treating colon cancer is the aim of modern medicine. Chalcones and their derivatives have shown an anticancer activity. The aim of the study was to evaluate the effect of methoxy-derivatives of 2'-hydroxychalcones: 2'-hydroxy-3"-methoxychalcone (TJ3), 2'-hydroxy-2"-methoxychalcone (TJ6) and 2'-hydroxy-4"-metoxychalcone (TJ7) at the concentrations of 10 µM and 25 µM on the release of IL-8, MIF, VCAM-1, ICAM-1 by colon cancer SW480 and SW620 cell lines. The cytokines and adhesion molecules were detected using the Bio-Plex Magnetic Luminex Assay and the Bio-Plex Suspension Array System. Our results showed that all tested methoxy-derivatives of 2'-hydroxychalcone compounds significantly reduced ICAM-1 released by SW480 cancer cells. The tested compounds at both concentrations did not significantly affect VCAM-1 released by SW480 and SW620 cancer cell lines. All methoxy-derivatives significantly reduced the concentration of MIF in dose dependent manner on SW480 cells. The TJ3 at the concentration of 25 µM significantly decreased IL-8 secreted by SW480 and SW620 cancer cells. Our results demonstrated that tested methoxy-derivatives of 2'-hydroxychalcones showed modulating effect on colon cancer cells.
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Affiliation(s)
- Joanna Bronikowska
- Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
| | - Małgorzata Kłósek
- Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
| | - Tomasz Janeczko
- Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
| | - Edyta Kostrzewa-Susłow
- Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
| | - Zenon P Czuba
- Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
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Bilgir F, Bilgir O, Akan OY, Demir I. Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism. ACTA ACUST UNITED AC 2020; 66:1057-1061. [PMID: 32935798 DOI: 10.1590/1806-9282.66.8.1057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 02/26/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.
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Affiliation(s)
- Ferda Bilgir
- . Katip Celebi University Ataturk Training and Research Hospital, Department of Allergy and Immunology, Izmir, Turkey
| | - Oktay Bilgir
- . Health Sciences University Bozyaka Training and Research Hospital, Department of Internal Medicine, Bozyaka, Izmir, Turkey
| | - Ozden Yildirim Akan
- . Health Sciences University Bozyaka Training and Research Hospital, Department of Internal Medicine, Bozyaka, Izmir, Turkey
| | - Ismail Demir
- . Health Sciences University Bozyaka Training and Research Hospital, Department of Internal Medicine, Bozyaka, Izmir, Turkey
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Zhou L, Zhang S, Zou X, Lu J, Yang X, Xu Z, Shan A, Jia W, Liu F, Yan X, Su H, Liang T, Zheng M, Zhang Y, Feng B. The β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) inhibits the colorectal cancer metastasis by stabilizing intercellular adhesion molecule-1 via sialylation. Cancer Manag Res 2019; 11:6185-6199. [PMID: 31308754 PMCID: PMC6613604 DOI: 10.2147/cmar.s208631] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 05/09/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Colorectal cancer (CRC) is one of the most frequent malignancies of the digestive system. Elevated expression of β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) has been observed in multiple cancers. But the mechanism of how ST6GAL1 might affect cancer cells remains to be clarified. Our previous study recognized intercellular adhesion molecule-1(ICAM-1) as a probable substrate of ST6GAL1 through mass spectrometry (MS) analysis. ICAM-1 is related to tumor metastasis in various cancers. Methods: First, ST6GAL1 was overexpressed and knocked down to perform transwell and wound healing assays, and the results were further confirmed in vivo. Based on the results of MS, GO and KEGG analysis were applied to reveal the connection between ST6GAL1 and ICAM-1. Immunoblot and tissue microarrays were administered to investigate the expression of ICAM-1 in different stages of CRC. Next, PCR, lectin precipitation and cycloheximide (CHX) were used to demonstrate the mechanism of ST6GAL1 on ICAM-1. Moreover, we investigated the sialylation on soluble ICAM in serum and its connection to tumor staging. Results: Overexpression of ST6GAL1 inhibited the migratory ability, while knockdown of ST6GAL1 cells had the reverse effect. Moreover, nude mice injected with ST6GAL1-knockdown cells harvested more liver metastases. Based on the GO and KEGG analysis, data from TCGA database showed a positive correlation between ST6GAL1 and ICAM-1. ICAM-1 also demonstrated a significant decrease in stage III/IV compared with stage I/II tumors. Our results revealed that ST6GAL1 could increase the stability of ICAM-1 through sialylation but had little influence on transcriptional level. Additionally, results of serum lectin precipitation revealed a correlation between the level of sialylation on soluble ICAM and CRC staging. Conclusion: This study illustrated that ST6GAL1 inhibited the metastatic ability of CRC by stabilizing ICAM-1 via sialylation and demonstrated a correlation between CRC staging and the sialylation on soluble ICAM-1 in serum.
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Affiliation(s)
- Leqi Zhou
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Sen Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Xia Zou
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Jishun Lu
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Xiao Yang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Zhijue Xu
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Aidong Shan
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Wenjuan Jia
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Feng Liu
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Xialin Yan
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Hao Su
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Tao Liang
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Minhua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yan Zhang
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Bo Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.,Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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Krisp C, Parker R, Pascovici D, Hayward NK, Wilmott JS, Thompson JF, Mann GJ, Long GV, Scolyer RA, Molloy MP. Proteomic phenotyping of metastatic melanoma reveals putative signatures of MEK inhibitor response and prognosis. Br J Cancer 2018; 119:713-723. [PMID: 30116025 PMCID: PMC6173697 DOI: 10.1038/s41416-018-0227-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 07/17/2018] [Accepted: 07/19/2018] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Genotyping of melanomas is used to identify patients for treatment with BRAF and MEK inhibitors, but clinical responses are highly variable. This study investigated the utility of protein expression phenotyping to provide an integrated assessment of gene expression programs in BRAF/NRAS melanoma which would be useful for prognosis and may predict response to MEK inhibition. METHODS Mass spectrometry profiling of early passage cell lines established from Stage III cutaneous melanomas was conducted. Basal protein expression was correlated with in vitro response to the MEK inhibitor, selumetinib. Protein expression in a cohort of 32 drug naïve BRAF/NRAS metastatic melanoma specimens was examined. The prognostic utility of a subset of these proteins and mRNA transcripts from a separate cohort was determined. RESULTS Unsupervised analysis of basal cell line protein abundances delineated response to selumetinib, but BRAF/NRAS genotype did not. Resistance was associated with functions including cell motility, cell adhesion and cytoskeletal organization. Several of these response biomarkers were observed in lymph node biospecimens and correlated with melanoma-specific survival. Loss of ICAM-1 protein and mRNA expression was a strong prognosticator of diminished survival in BRAF/NRAS mutant melanoma. CONCLUSIONS These results demonstrate the utility of proteomic phenotyping to identify both putative biomarkers of response to MEK inhibition and prognostication associated with metastatic melanoma.
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Affiliation(s)
- Christoph Krisp
- Australian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
- University Medical Center Hamburg, Institute for Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics Group, Hamburg, Germany
| | - Robert Parker
- Australian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
| | - Dana Pascovici
- Australian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
| | - Nicholas K Hayward
- Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - James S Wilmott
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
| | - John F Thompson
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Graham J Mann
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
| | - Georgina V Long
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - Richard A Scolyer
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Mark P Molloy
- Australian Proteome Analysis Facility (APAF), Department of Chemistry & Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia.
- Kolling Institute, The University of Sydney, Sydney, NSW, Australia.
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Rutherford EJ, Hill ADK, Hopkins AM. Adhesion in Physiological, Benign and Malignant Proliferative States of the Endometrium: Microenvironment and the Clinical Big Picture. Cells 2018; 7:E43. [PMID: 29772648 PMCID: PMC5981267 DOI: 10.3390/cells7050043] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 05/09/2018] [Accepted: 05/11/2018] [Indexed: 12/13/2022] Open
Abstract
Although the developments in cellular and molecular biology over the last few decades have significantly advanced our understanding of the processes and players that regulate invasive disease, many areas of uncertainty remain. This review will discuss the contribution of dysregulated cell⁻cell and cell⁻matrix adhesion to the invasion in both benign and malignant contexts. Using the endometrium as an illustrative tissue that undergoes clinically significant invasion in both contexts, the adhesion considerations in the cells ("seed") and their microenvironment ("soil") will be discussed. We hope to orientate this discussion towards translational relevance for the diagnosis and treatment of endometrial conditions, which are currently associated with significant morbidity and mortality.
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Affiliation(s)
- Emily J Rutherford
- Department of Surgery, Royal College of Surgeons in Ireland, RCSI Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
| | - Arnold D K Hill
- Department of Surgery, Royal College of Surgeons in Ireland, RCSI Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
| | - Ann M Hopkins
- Department of Surgery, Royal College of Surgeons in Ireland, RCSI Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
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10
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Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers? Biomed Pharmacother 2016; 77:86-91. [PMID: 26796270 DOI: 10.1016/j.biopha.2015.12.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Revised: 11/26/2015] [Accepted: 12/11/2015] [Indexed: 12/19/2022] Open
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11
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de Aquino MTP, Malhotra A, Mishra MK, Shanker A. Challenges and future perspectives of T cell immunotherapy in cancer. Immunol Lett 2015; 166:117-33. [PMID: 26096822 PMCID: PMC4499494 DOI: 10.1016/j.imlet.2015.05.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Revised: 05/10/2015] [Accepted: 05/27/2015] [Indexed: 12/15/2022]
Abstract
Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signalling. An inhibitory cytokine milieu in the tumour microenvironment also leads to immune suppression and tumour progression within a host. This review traces the development in the field and attempts to summarize the hurdles that the approach of adoptive T cell immunotherapy against cancer faces, and discusses the conditions that must be improved to allow effective eradication of cancer.
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Affiliation(s)
- Maria Teresa P de Aquino
- Department of Biochemistry and Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA
| | - Anshu Malhotra
- Department of Biochemistry and Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA
| | - Manoj K Mishra
- Department of Biological Sciences, Alabama State University, Montgomery, AL 36101, USA
| | - Anil Shanker
- Department of Biochemistry and Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA; Tumor-Host Interactions Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
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12
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Dias MMDS, Noratto G, Martino HSD, Arbizu S, Peluzio MDCG, Talcott S, Ramos AM, Mertens-Talcott SU. Pro-apoptotic activities of polyphenolics from açai (Euterpe oleracea Martius) in human SW-480 colon cancer cells. Nutr Cancer 2014; 66:1394-405. [PMID: 25329001 DOI: 10.1080/01635581.2014.956252] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
This study aimed to evaluate the cell growth inhibition activity of açai (Euterpe oleracea Mart.) polyphenolic extract against colon cancer HT-29 and SW-480 cells and the nonmalignant CCD-18Co colon fibroblast cells. Results showed that açai polyphenolic extract (5-20 mg/L) inhibited preferentially the growth of SW-480 cells with no toxicity in CCD-18Co cells, and this was accompanied by reduction of H2O2-induced reactive oxygen species (ROS) generation. The mechanisms involved in SW-480 cell growth-inhibition by açai polyphenolic extract included the downregulation of NF-κB proinflammatory transcription factor and the nuclear factor-kappa B targets intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, prooncogenic specificity proteins (Sp) were downregulated as well as Sp-targets Bcl-2, vascular endothelial growth factor, and survivin. This was accompanied by activation of mitochondrial proapoptotic pathway involving increase of cytochrome c, cleavage of caspase-3, and decrease of PARP-1. Results strongly suggest that açai polyphenolic extract has antiinflammatory and cytotoxic activities in colon cancer cells and can be effective as natural colon cancer chemopreventive agents.
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13
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Kaplan MA, Kucukoner M, Inal A, Urakci Z, Evliyaoglu O, Firat U, Kaya M, Isikdogan A. Relationship between serum soluble vascular adhesion protein-1 level and gastric cancer prognosis. Oncol Res Treat 2014; 37:340-4. [PMID: 24903765 DOI: 10.1159/000362626] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 04/02/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. The prognostic importance of VAP-1 was determined in various human cancers. The aim of this study was to determine the relationship between VAP-1 and prognosis of gastric cancer. MATERIALS AND METHODS Serum of operable and metastatic gastric cancer patients was collected before treatment (surgery, radiotherapy, and/or chemotherapy). VAP-1 levels were measured by enzyme-linked immunosorbent assay. RESULTS A total of 86 gastric cancer patients (32 female, 54 male) were included in the study. Curative surgical treatment was performed in 54 (62.8%) patients. The mean serum VAP-1 level was 324.4 pg/ml and significantly higher in operable gastric cancer patients compared to metastatic gastric cancer patients (383.1 ± 173.5 vs. 225.2 ± 113.9 pg/ml; p < 0.001). When a cut-off value for VAP-1 of 218.8 pg/ml was determined by receiver operating characteristic (ROC) curves for presence of metastasis, sensitivity and specificity were 81.5 and 65.6%, respectively. Patients with decreased VAP-1 levels had a significantly poorer prognosis compared to patients with increased serum VAP-1 levels (median survival 8.2 vs. 23.5 months; p < 0.001). Multivariate analysis showed that VAP-1 is an independent prognostic factor of gastric cancer (odds ratio 2.3, 95% confidence interval 1.1-4.9; p = 0.032). CONCLUSION A low serum VAP-1 level may be an indicator of poor prognosis in gastric cancer. This study demonstrated that low serum VAP-1 levels are associated with poor prognosis in gastric cancer patients.
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Affiliation(s)
- Muhammet A Kaplan
- Department of Medical Oncology, School of Medicine, Dicle University, Diyarbakir, Turkey
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14
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Tognarelli S, Gayet J, Lambert M, Dupuy S, Karras A, Cohen P, Guillevin L, de Menthon M, Caillat-Zucman S. Tissue-specific microvascular endothelial cells show distinct capacity to activate NK cells: implications for the pathophysiology of granulomatosis with polyangiitis. THE JOURNAL OF IMMUNOLOGY 2014; 192:3399-408. [PMID: 24600034 DOI: 10.4049/jimmunol.1301508] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The relevance of tissue specificity of microvascular endothelial cells (MECs) in the response to inflammatory stimuli and sensitivity to immune cell-mediated injury is not well defined. We hypothesized that such MEC characteristics might shape their interaction with NK cells through the use of different adhesion molecules and NK cell receptor ligands or the release of different soluble factors and render them more or less vulnerable to NK cell injury during autoimmune vasculitis, such as granulomatosis with polyangiitis (GPA). To generate a comprehensive expression profile of human MECs of renal, lung, and dermal tissue origin, we characterized, in detail, their response to inflammatory cytokines and to proteinase 3, a major autoantigen in GPA, and analyzed the effects on NK cell activation. In this study, we show that renal MECs were more susceptible than lung and dermal MECs to the effect of inflammatory signals, showing upregulation of ICAM-1 and VCAM-1 on their surface, as well as release of CCL2, soluble fractalkine, and soluble VCAM-1. Proteinase 3-stimulated renal and lung MECs triggered CD107a degranulation in control NK cell. Notably, NK cells from GPA patients expressed markers of recent in vivo activation (CD69, CD107a), degranulated more efficiently than did control NK cells in the presence of renal MECs, and induced direct killing of renal MECs in vitro. These results suggest that, upon inflammatory conditions in GPA, renal MECs may contribute to the recruitment and activation of NK cells in the target vessel wall, which may participate in the necrotizing vasculitis of the kidney during this disease.
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Affiliation(s)
- Sara Tognarelli
- INSERM, U1016 Hôpital Saint-Vincent de Paul, 75014 Paris, France
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15
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Schellerer VS, Langheinrich M, Hohenberger W, Croner RS, Merkel S, Rau TT, Stürzl M, Naschberger E. Tumor-associated fibroblasts isolated from colorectal cancer tissues exhibit increased ICAM-1 expression and affinity for monocytes. Oncol Rep 2013; 31:255-61. [PMID: 24253852 DOI: 10.3892/or.2013.2860] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Accepted: 09/27/2013] [Indexed: 02/07/2023] Open
Abstract
Progression of colorectal cancer (CRC) is strongly associated with inflammation and other desmoplastic reactions in the tumor cell-surrounding tissue. We successfully isolated fibroblasts from the desmoplastic stroma of human CRC specimens and uninvolved colon tissue of patients treated surgically for CRC and investigated potential functional capacities. All of the isolated fibroblasts were vimentin-positive and CK-20/CD45-negative confirming the fibroblast phenotype. Differential expression patterns were detected between tumor-associated fibroblasts (TAFs) and normal tissue-associated fibroblasts (NAFs) regarding intercellular adhesion molecule-1 (ICAM-1) expression. In 11 of 12 TAF cultures, basal ICAM-1 expression was increased as compared to corresponding NAF cultures (p=0.001). After stimulation of the cultures with interleukin-1β, 8 of the 12 TAF cultures presented higher ICAM-1 levels when compared with the level in the corresponding NAF cultures (p=0.001). Moreover, the adhesive capacity of these cultures for U937 was increased in 8 out of 10 unstimulated and in 10 out of 10 stimulated cultures when TAFs and NAFs were compared. In corresponding tumor tissue sections from the same patients, the amount of ICAM-1-positive fibroblasts was significantly higher than that in the corresponding normal colon mucosa, indicating a tumor-specific effect that was maintained in the isolated cultures. These results indicate that fibroblasts from CRC tissue exhibit an increased affinity for monocytic cells. This increased intercellular interaction may contribute to elongated residence times of monocytes in CRC tissue. Therefore, these isolated fibroblasts are a useful tool for further functional investigation of desmoplastic tissue reactions in CRC.
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Affiliation(s)
- Vera S Schellerer
- Department of Surgery, University Medical Center Erlangen, D-91054 Erlangen, Germany
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16
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Jung WC, Jang YJ, Kim JH, Park SS, Park SH, Kim SJ, Mok YJ, Kim CS. Expression of intercellular adhesion molecule-1 and e-selectin in gastric cancer and their clinical significance. J Gastric Cancer 2012; 12:140-8. [PMID: 23094225 PMCID: PMC3473220 DOI: 10.5230/jgc.2012.12.3.140] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Revised: 08/09/2012] [Accepted: 08/10/2012] [Indexed: 01/25/2023] Open
Abstract
Purpose Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. Materials and Methods The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. Results In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). Conclusions Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.
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Affiliation(s)
- Woo-Chul Jung
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
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17
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How do tumors actively escape from host immunosurveillance? Arch Immunol Ther Exp (Warsz) 2010; 58:435-48. [PMID: 20922572 DOI: 10.1007/s00005-010-0102-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2010] [Accepted: 05/28/2010] [Indexed: 12/12/2022]
Abstract
The immunological background for the process of tumor growth is still obscure. However, our understanding of what happens could have important consequences, namely in the context of cancer immunotherapy. A tumor is able to grow in the host environment either because it is recognizable as normal tissue and tolerated by host immune cells, or because it can "escape" from host immunosurveillance. According to the second option the mechanisms of tumor recognition and consequent destruction are actively disturbed by such processes as: change of tumor immunogenicity, production of tumor-derived regulatory molecules, and interaction of cancer cells with tumor-infiltrating immune cells. The results of studies devoted to the problem of immunoregulation in the tumor environment seem to support the "escape" hypothesis.
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18
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Serum sICAM, sVCAM and sE-selectin levels in colorectal cancer patients. Folia Histochem Cytobiol 2010; 47:621-5. [PMID: 20430730 DOI: 10.2478/v10042-009-0077-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and the fourth cause of cancers death in the world. Soluble adhesion molecules (CAMs) are thought to have an important role in host defense against carcinogenesis. They are biomarkers of inflammation and indicators of the immune response to tumors. The study included 40 CRC patients without remote metastases and 24 control subjects. Serum concentrations of sE-selectin, sICAM and sVCAM in patients with CRC were investigated by ELISA method. The level of the sCAMs decreased significantly after radical tumor resection. Preoperative serum concentrations of sICAM and sVCAM in CRC patients were significantly higher compared to the control group, whereas there were no differences regarding serum sE-selectin. Serum levels of sE-selectin, sICAM and sVCAM correlated significantly with each other. There was a significant correlation of serum levels of sICAM-1 and sVCAM-1, but not sE-selectin, with TNM stage and lymph node involvement. No significant relationship was found between serum concentrations of sICAM-1, sVCAM-1 and sE-selectin in CRC patients and patients' age or gender. Our findings suggest that an improved understanding of the mechanisms of membrane shedding of sICAM, sVCAM and sE-selectin is required to delineate their role in tumor progression.
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19
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Yockell-Lelièvre J, Spriet C, Cantin P, Malenfant P, Heliot L, de Launoit Y, Audette M. Functional cooperation between Stat-1 and ets-1 to optimize icam-1 gene transcription. Biochem Cell Biol 2010; 87:905-18. [PMID: 19935876 DOI: 10.1139/o09-055] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the immune system, enabling the interactions between effector cells and target cells. It is also known to be involved in tumor growth and metastasis. Its expression is transcriptionally regulated by several proinflammatory cytokines including IFN-gamma, which induces ICAM-1 transcription via the JAK-STAT signaling pathway in a Stat1-dependent fashion. The ICAM-1 promoter contains several cis-active regulatory elements including 2 Ets binding sites (EBSs) located at positions -158 and -138 relatively to the AUG, which were previously shown to play a role in the constitutive activity of the ICAM-1 promoter. In the present study, we have determined whether the EBSs are also involved in the regulation of ICAM-1 gene transcription by pro-inflammatory cytokines. Transient transfection assays were performed with reporter genes containing ICAM-1 promoter constructions cloned upstream from the firefly luciferase gene. Site-specific mutations of the EBS diminished the promoter activity stimulated by IFN-gamma, although the IFN-gamma responsive element (pIgammaRE), which binds Stat1, was intact. Stimulation of the transcriptional activity following IFN-gamma treatment was significantly reduced when both EBSs were inactivated. Co-immunoprecipitation experiments provided evidence of a physical interaction involving Ets1 and Stat1. In COS-1 and HEK 293 cells cotransfected with CFP-Stat1 and YFP-Ets fusion protein, fluorescence resonance energy transfer experiments confirmed the close proximity of these 2 proteins in living cells following treatment with IFN-gamma.
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Affiliation(s)
- Julien Yockell-Lelièvre
- Centre de recherche en endocrinologie moléculaire et oncologique, Centre de recherche du CHUQ, Pavillon CHUL, 2705 boulevard Laurier, QC G1V 4G2, Canada
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20
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Toiyama Y, Miki C, Inoue Y, Kawamoto A, Kusunoki M. Circulating form of human vascular adhesion protein-1 (VAP-1): decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis. J Surg Oncol 2009; 99:368-72. [PMID: 19204971 DOI: 10.1002/jso.21246] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND AND OBJECTIVES Vascular adhesion protein-1 (VAP-1) is an endothelial cell molecule that controls leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) has been described in certain diseases with an inflammatory component. However, sVAP-1 expression or function has not been studied in colorectal cancer. The present study determined the relationships between preoperative serum sVAP-1 and clinicopathological features and prognosis in colorectal cancer. METHODS One hundred patients with histologically proven colorectal cancer and 33 normal volunteers were included. Preoperative serum was collected, and sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS Mean sVAP-1 level in patients was significantly higher than in controls, and decreased with disease progression. Mean sVAP-1 level was significantly correlated with venous invasion, lymph node metastasis, distant metastasis including hepatic metastasis, and advanced TNM classification. Furthermore, sVAP-1 was an independent marker for predicting lymph node or hepatic metastasis. Prognosis of patients with a lower sVAP-1 level was significantly worse than those with elevated sVAP-1. CONCLUSIONS Preoperative low sVAP-1 level is associated with poor prognosis in colorectal cancer. Measuring serum sVAP-1 may provide valuable information in predicting patients with lymph node or hepatic metastasis.
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Affiliation(s)
- Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
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21
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Immunosuppressive mechanisms in human tumors: why we still cannot cure cancer. Immunol Lett 2007; 116:7-14. [PMID: 18164076 DOI: 10.1016/j.imlet.2007.11.012] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2007] [Revised: 11/02/2007] [Accepted: 11/09/2007] [Indexed: 12/29/2022]
Abstract
Tumor cells often evoke specific immune responses that, however, fail to eliminate all the tumor cells. The development of cancer immunotherapies is, therefore, mostly focused on the generation of large numbers of activated anti-tumor effector cells by vaccination or adoptive T cell transfer. These developments are built on an ever-extended list of identified tumor-associated antigens and corresponding T cell epitopes, and a steady flow of reports from proof-of-principle animal model experiments demonstrating cure from disease by immune interventions. However, the promises have not translated into clinical successes for cancer patients. Even where tumor regression or complete responses were achieved there is usually relapse of the disease. Increasing numbers of reports over recent years highlight potential immunosuppressive mechanisms that act in tumors and systemically in cancer patients to block effective anti-tumor immune responses. They account in large parts for the failures of cancer immunotherapy and need to be overcome before progress can be expected. We review here the current state of the research on immunosuppressive networks in human cancer.
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22
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Abstract
Even though liver metastasis accounts for the vast majority of cancer deaths in patients with colorectal cancer (CRC), fundamental questions about the molecular and cellular mechanisms of liver metastasis still remain unanswered. Determination of gene expression profiles by microarray technology has improved our knowledge of CRC molecular pathways. However, defined gene signatures are highly variable among studies. Expression profiles and molecular markers have been specifically linked to liver metastases mechanistic paths in CRC. However, to date, none of the identified signatures or molecular markers has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. To obtain a genetic signature for liver metastasis in CRC, measures to improve reproducibility, to increase consistency, and to validate results need to be implemented. Alternatives to expression profiling with microarray technology are continuing to be used. In the recent past, many genes codifying for proteins that are directly or indirectly involved in adhesion, invasion, angiogenesis, survival and cell growth have been linked to mechanisms of liver metastases in CRC.
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23
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Guney N, Soydinc HO, Derin D, Tas F, Camlica H, Duranyildiz D, Yasasever V, Topuz E. Serum levels of intercellular adhesion molecule ICAM-1 and E-selectin in advanced stage non-small cell lung cancer. Med Oncol 2007; 25:194-200. [PMID: 18008189 DOI: 10.1007/s12032-007-9026-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2007] [Accepted: 10/20/2007] [Indexed: 10/22/2022]
Abstract
Cell adhesion is a basic count in inter- and intra-cellular communication and plays an important role in tumor progression. This study was conducted to investigate the serum levels of intercellular adhesion molecule (ICAM-1) and E-selectin in patients with advanced stage non-small cell lung cancer (NSCLC) and the relationships with known prognostic parameters and therapy. These serum factors were measured of 57 NSCLC patients pathologically verified before and after chemotherapy in comparison with 24 healthy controls by using ELISA method. Serum levels of ICAM-1 were increased significantly in NSCLC patients compared with the healthy controls (P = 0.006). However, serum E-selectin levels were not significantly different from healthy control groups (0.643). No statistically significant relationships were found between investigated all serum parameters and various characteristics of patients, and the diseases such as stage and tumor burden. Likewise, we also found no correlation between serum ICAM-1 and E-selectin (P = 0.78). We found that serum ICAM-1 levels were decreased owing to the chemotherapy effect, independently from chemotherapy response. However, serum E-selectin levels were not changed by the chemotherapy effect. The median survival of all patients was 11.9 months and 1-year survival rate was 47.6%. We found that patients performance status (P = 0.013), age (P = 0.015), and weight loss (P = 0.007) were prognostic factors for survival. Serum E-selectin levels showed a trend (P = 0.08) related to worse prognosis, however serum ICAM-1 levels were determined as ineffective on survival (P = 0.11). Multivariate analysis revealed that only weight loss (P = 0.005) and E-selectin levels (P = 0.002) remained as an independent prognostic factor for survival in patients with advanced NSCLC. In conclusion, our data suggest that higher serum ICAM-1 can be useful for diagnosis while E-selectin levels have prognostic significance and could be a potential prognostic factor in NSCLC patients.
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Affiliation(s)
- Nese Guney
- Institute of Oncology, Istanbul University, 34390 Istanbul, Turkey.
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24
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Morandi F, Levreri I, Bocca P, Galleni B, Raffaghello L, Ferrone S, Prigione I, Pistoia V. Human Neuroblastoma Cells Trigger an Immunosuppressive Program in Monocytes by Stimulating Soluble HLA-G Release. Cancer Res 2007; 67:6433-41. [PMID: 17616704 DOI: 10.1158/0008-5472.can-06-4588] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
HLA-G is overexpressed in different tumors and plays a role in immune escape. Because no information is available on HLA-G in relation to human neuroblastoma, we have investigated the expression of membrane-bound and secretion of soluble isoforms of HLA-G in neuroblastoma and functionally characterized their immunosuppressive activities. At diagnosis, serum soluble HLA-G (sHLA-G) levels were significantly higher in patients than in age-matched healthy subjects. In addition, patients who subsequently relapsed exhibited higher sHLA-G levels than those who remained in remission. Neuroblastoma patient sera selected according to high sHLA-G concentrations inhibited natural killer (NK) cell and CTL-mediated neuroblastoma cell lysis. Such lysis was partially restored by serum depletion of sHLA-G. In 6 of 12 human neuroblastoma cell lines, low HLA-G surface expression was not up-regulated by IFN-gamma. Only the ACN cell line secreted constitutively sHLA-G. IFN-gamma induced de novo sHLA-G secretion by LAN-5 and SHSY5Y cells and enhanced that by ACN cells. Primary tumor lesions from neuroblastoma patients tested negative for HLA-G. Neuroblastoma patients displayed a higher number of sHLA-G-secreting monocytes than healthy controls. Incubation of monocytes from normal donors with IFN-gamma or pooled neuroblastoma cell line supernatants significantly increased the proportion of sHLA-G-secreting cells. In addition, tumor cell supernatants up-regulated monocyte expression of CD68, HLA-DR, CD69, and CD71 and down-regulated IL-12 production. Our conclusions are the following: (a) sHLA-G serum levels are increased in neuroblastoma patients and correlate with relapse, (b) sHLA-G is secreted by monocytes activated by tumor cells rather than by tumor cells themselves, and (c) sHLA-G dampens anti-neuroblastoma immune responses.
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Affiliation(s)
- Fabio Morandi
- Laboratory of Oncology, G. Gaslini Children's Hospital, Genoa, Italy.
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25
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Ke JJ, Shao QS, Ling ZQ. Expression of E-selectin, integrin β 1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance. World J Gastroenterol 2006; 12:3609-11. [PMID: 16773720 PMCID: PMC4087579 DOI: 10.3748/wjg.v12.i22.3609] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To study the expression levels of E- selectin, integrin β1 and immunoglobulin supperfamily member-intercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma.
METHODS: The serum contents of E-selectin, integrin β1 and ICAM-1 were detected by enzyme-linked immunosorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation.
RESULTS: The serum E-selectin, ECAM-1 and integrin β1 were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrin β1 were significantly higher in gastric carcinoma patients than in controls (P < 0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant difference (P = 0.64). In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients.
CONCLUSION: Serum E-selectin, ICAM-1 and integrin β1 expression levels are probably related to the metastasis and relapse of gastric cancer.
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Affiliation(s)
- Jin-Jing Ke
- Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
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26
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Coskun U, Sancak B, Sen I, Bukan N, Tufan MA, Gülbahar O, Sozen S. Serum P-selectin, soluble vascular cell adhesion molecule-I (s-VCAM-I) and soluble intercellular adhesion molecule-I (s-ICAM-I) levels in bladder carcinoma patients with different stages. Int Immunopharmacol 2006; 6:672-7. [PMID: 16504931 DOI: 10.1016/j.intimp.2005.10.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2005] [Revised: 09/11/2005] [Accepted: 10/19/2005] [Indexed: 11/30/2022]
Abstract
Adhesion molecules are thought to have a role in the host defense against carcinogenesis. In this study, we measured serum platelet-(P-) selectin, soluble vascular cell adhesion molecule-I (s-VCAM-I), and soluble intercellular adhesion molecule-I (s-ICAM-I) levels in 51 sequential bladder cancer patients at our urology clinic and 8 controls. Serum levels of P-selectin, s-VCAM-I and s-ICAM-I were significantly higher in all patients than controls. Serum P-selectin and s-ICAM-I levels did not differ based on tumor (T) stage and tumor grade, whereas serum levels of s-VCAM-I were significantly higher in patients with muscle invasive tumors than those with superficial tumors. Further, s-VCAM-I levels correlated with T stage. In conclusion, significantly increased P-selectin, s-VCAM-I, and s-ICAM-I levels were observed in patients with bladder cancer, and s-VCAM-I levels correlated with T stage. Thus, we suggest that the analysis of serum s-VCAM-I levels may provide a prognostic test for T stage and bladder cancer progression during and/or following therapy.
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Affiliation(s)
- Ugur Coskun
- Gazi University Medical School, Department of Medical Oncology, Ankara, Turkey.
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27
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Kamezaki S, Kurozawa Y, Iwai N, Hosoda T, Okamoto M, Nose T. Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer. Eur J Cancer 2005; 41:2355-9. [PMID: 16146689 DOI: 10.1016/j.ejca.2005.07.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2005] [Revised: 06/14/2005] [Accepted: 07/05/2005] [Indexed: 11/26/2022]
Abstract
To investigate whether serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were related to first stage cancer before diagnosis of cancer, we compared serum levels of these adhesion molecules between pre-clinical cases and controls using a nested case-control study method. Cancer cases were recruited from a cohort database of 1465 participants who completed a baseline questionnaire and provided blood samples, and were followed up from 1989 to 2003. They consisted of 15 individuals who died of cancer and 31 individuals newly diagnosed with cancer during the follow-up period. Controls were subjects who did not suffer from cancer, cerebral apoplexy, diabetes mellitus, liver disease, or myocardial infarction during the follow-up period. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits, we showed that serum levels of sVCAM-1, but not sICAM-1 were elevated in cases with pre-clinical or early cancer. We suggest that elevated serum levels of sVCAM-1 might serve as a possible marker for detecting pre-clinical or early cancer.
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Affiliation(s)
- Sachiko Kamezaki
- Division of Human Living Sciences, Tottori College, 854 Fukuba, Kurayoshi, Tottori 682-8555, Japan.
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Alexiou D, Karayiannakis AJ, Syrigos KN, Zbar A, Sekara E, Michail P, Rosenberg T, Diamantis T. Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am J Gastroenterol 2003; 98:478-85. [PMID: 12591072 DOI: 10.1111/j.1572-0241.2003.07259.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.
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Affiliation(s)
- Dimitrios Alexiou
- First Department of Surgery, University of Athens, Medical School, Greece
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Fiore E, Fusco C, Romero P, Stamenkovic I. Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity. Oncogene 2002; 21:5213-23. [PMID: 12149643 DOI: 10.1038/sj.onc.1205684] [Citation(s) in RCA: 165] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2001] [Revised: 05/15/2002] [Accepted: 05/20/2002] [Indexed: 01/21/2023]
Abstract
Shedding of intercellular adhesion molecule 1 (ICAM-1) is believed to play a role in tumor cell resistance to cell-mediated cytotoxicity. However, the mechanism whereby ICAM-1 is shed from the surface of tumor cells remains unclear. In this study, we have addressed the possibility that matrix metalloproteinases are implicated in ICAM-1 shedding. Our observations suggest a functional relationship between ICAM-1 and matrix metalloproteinase 9 (MMP-9) whereby ICAM-1 provides a cell surface docking mechanism for proMMP-9, which, upon activation, proteolytically cleaves the extracellular domain of ICAM-1 leading to its release from the cell surface. MMP-9-dependent shedding of ICAM-1 is found to augment tumor cell resistance to natural killer (NK) cell-mediated cytotoxicity. Taken together, our observations propose a mechanism for ICAM-1 shedding from the cell surface and provide support for MMP involvement in tumor cell evasion of immune surveillance.
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Affiliation(s)
- Emilio Fiore
- Molecular Pathology Unit and MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, MA 02129, USA
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30
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Maruo Y, Gochi A, Kaihara A, Shimamura H, Yamada T, Tanaka N, Orita K. ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int J Cancer 2002; 100:486-90. [PMID: 12115535 DOI: 10.1002/ijc.10514] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
ICAM-1 plays an important role in cell-cell and cell-extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM-1 expression by cancer cells or the serum level of s-ICAM-1 was (s-ICAM-1) was examined. ICAM-1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM-1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node-negative and 56.1% in node-positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s-ICAM-1 level was 262.1 ng/ml (median 205.5, range 176.0-271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7-1,768.0) in gastric cancer patients (p < 0.001). The serum s-ICAM-1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM-1 expression cases had significantly higher s-ICAM-1 levels than negative ones, 408.9 +/- 188.4 and 308.1 +/- 88.1 ng/ml, respectively. These results suggested that ICAM-1 was overexpressed in cancer cells and released as s-ICAM-1, which would promote hematogenous metastasis by suppressing local anticancer immunity.
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Affiliation(s)
- Yukinobu Maruo
- First Department of Surgery, Okayama University Medical School, Okayama, Japan
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31
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Alexiou D, Karayiannakis AJ, Syrigos KN, Zbar A, Kremmyda A, Bramis I, Tsigris C. Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery. Eur J Cancer 2001; 37:2392-7. [PMID: 11720833 DOI: 10.1016/s0959-8049(01)00318-5] [Citation(s) in RCA: 127] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The serum concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin, ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage, for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management.
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Affiliation(s)
- D Alexiou
- First Department of Surgery, University of Athens, Medical School, Athens, Greece
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Abstract
INTRODUCTION This review was aimed at summarizing recent advances in the understanding of cell adhesion in order to discuss the possible relevance of new knowledge to the exploration of cancer patients and elaboration of therapeutic strategies. CURRENT KNOWLEDGE AND KEY POINTS During the last 10 years, many adhesion molecules were identified, thus allowing to determine their tissue distribution and functional regulation. The concept of adhesiveness was refined. It is now well known that adhesive rate (i.e., the minimal contact time required for bond formation) and binding strength (i.e., the minimal force required to detach bound cells) are distinct parameters. They may be regulated independently, and influence the cell behavior in different ways. It is now possible to achieve accurate control of tumor cell adhesiveness, either by inhibiting an adhesive mechanism (through monoclonal antibodies, competitive ligands, or inhibition of receptor expression with antisense strategy or gene knock-out) or by promoting a binding mechanism (with receptor transfection or pro-inflammatory stimulation). FUTURE PROSPECTS AND PROJECTS Recent progress opens new possibilities for diagnosis and treatment. First, the interpretation of experimental data may be improved. Cell adhesive behavior is not entirely accounted for by the density of membrane adhesion receptors. Indeed, adhesion is influenced by receptor connection to the cytoskeleton and structure of the cell coat. An adhesion receptor may be anti-metastatic through an increase in tumor cohesion and cell differentiation, or pro-metastatic, through facilitation of cell migration towards a target tissue. New therapeutic strategies may include anti-adhesive procedure aimed at preventing metastasis formation. The potential importance of a better control of inflammatory processes is also emphasized in view of the influence of these processes on the expression of adhesion molecules.
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Affiliation(s)
- A Pierres
- Laboratoire d'immunologie, Unité Inserm 387, Hôpital de Sainte-Marguerite, Marseille, France
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Alexander CL, Edward M, MacKie RM. The role of human melanoma cell ICAM-1 expression on lymphokine activated killer cell-mediated lysis, and the effect of retinoic acid. Br J Cancer 1999; 80:1494-500. [PMID: 10408388 PMCID: PMC2363163 DOI: 10.1038/sj.bjc.6690551] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Intercellular adhesion molecule (ICAM-1) exists as a membrane-associated form (mICAM-1) on the surface of tumour cells as well as a soluble form (sICAM-1). This study analyses the ability of all-trans retinoic acid (RA) to alter both sICAM and mICAM-1 expression in C8161 and Hs294T human melanoma cell lines and investigates the involvement of ICAM-1 in the interaction between tumour and lymphokine-activated killer (LAK) cells using the Cr-51 release assay. Our data showed that 4-day pretreatment of the tumour cells with 10(-7) M RA and 10(-6) M RA induced an increase in lysis of both cell lines and also increased mICAM-1 expression without having any effect on sICAM-1 levels. Addition of blocking ICAM-1 antibody (10 microg ml(-1)) to the C8161 cells at an effector:tumour cell ratio of 40:1 caused a 2.3-fold reduction in lysis of tumour cells and a 3-fold reduction in lysis of RA-treated cells. Blocking ICAM-1 antibody at optimum concentrations of 5 microg ml(-1) reduced lysis 1.8-fold in control Hs294T cells and 1.3-fold in RA-treated cells. Blocking the HLA-ABC complex had no effect on lysis. The more highly metastatic C8161 cells were found to secrete 4-fold greater levels of sICAM-1 than the poorly metastatic Hs294T cells and addition of sICAM-1 to the assay failed to affect lysis of either cell line but did induce a 2-fold decrease in lysis of RA-treated C8161 cells. Collectively, these data provide further evidence for ICAM-1 involvement in the tumour/LAK cell response and indicates that the RA-induced increase in mICAM-1 levels are partly responsible for the increase in susceptibility of the tumour cells. sICAM-1 appears to be unimportant in evasion of the tumour cells from LAK cell lysis, but may play a role in evasion of RA-treated C8161 cells.
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Affiliation(s)
- C L Alexander
- Department of Dermatology, University of Glasgow, UK
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Takizawa K, Kamijo R, Ito D, Hatori M, Sumitani K, Nagumo M. Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorouracil in a cancer cell line via a NF-kappaB independent pathway. Br J Cancer 1999; 80:954-63. [PMID: 10362102 PMCID: PMC2363043 DOI: 10.1038/sj.bjc.6690449] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Cisplatin (CDDP) and 5-fluorouracil (5-FU) are common anti-tumour agents, and the anti-tumour effect of CDDP and 5-FU are synergistically enhanced by combined treatment. To clarify the mechanisms of this synergism, we examined the effect of CDDP and 5-FU on the expression of cell adhesion molecules involved in recognition of cancer cells by T lymphocytes. When NA cells, a squamous cell carcinoma cell line, were exposed to CDDP and 5-FU for 18 h, the expression of intercellular adhesion molecule-1 (ICAM-1) was synergistically induced, whereas CDDP or 5-FU alone did not induce the expression of ICAM-1, as determined by flow cytometry. Expression of ICAM-2 and ICAM-3, which are recognized by the same counter receptor on T-cells, were not up-regulated by CDDP and 5-FU. RT-PCR analysis showed that the induction of ICAM-1 on NA cells might be due to transcriptional induction of ICAM-1 mRNA. Treatment with genistein, a protein tyrosine kinase (PTK) inhibitor, inhibited the induction of ICAM-1 on NA cells by CDDP and 5-FU, whereas staurosporin, a protein kinase C inhibitor, did not. Although CDDP and 5-FU induced binding at the nuclear factor kappa B (NF-kappaB) site in the ICAM-1 promoter, pretreatment with genistein did not prevent CDDP and 5-FU-induced binding at the NF-kappaB site. Moreover, a NF-kappaB nuclear translocation inhibitor did not inhibit the induction of ICAM-1 expression by treatment with CDDP and 5-FU. The synergistic effect of CDDP and 5-FU was not specific to NA cells, since ICAM-1 was synergistically induced by CDDP and 5-FU on HSC-4 cells, a squamous cell carcinoma cell line. These findings indicate that treatment with CDDP and 5-FU induces ICAM-1 expression by a NF-kappaB independent regulatory mechanism involving PTK.
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Affiliation(s)
- K Takizawa
- Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan
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