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Qian S, He Y, Li R, Sun P, Zhang X, Pan L, Xu Z, Feng Z, Lian R, Yu L. Polymeric immunoglobulin receptor (pIgR) in cancer progression: a critical role and potential therapeutic target. Apoptosis 2025:10.1007/s10495-025-02116-x. [PMID: 40415061 DOI: 10.1007/s10495-025-02116-x] [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] [Accepted: 04/07/2025] [Indexed: 05/27/2025]
Abstract
Polymeric immunoglobulin receptor (pIgR) is a crucial receptor that primarily mediates the transcytosis of immunoglobulins A and M across epithelial cells, emerging as an essential participant in modulating both mucosal immunity and innate immunity. Recently, pIgR dysregulation in cancer has garnered widespread attention. It exhibits distinct mechanisms and effects across various cancer types with significant clinical value as a biomarker for malignant tumor diagnosis and prognosis evaluation. Recent therapeutic advances have revealed promising strategies, including dimeric IgA-based approaches targeting intracellular oncogenic drivers through pIgR-mediated transcytosis, small molecule modulators such as bufalin, and targeting EV-pIgR with neutralizing antibodies. Integrating these approaches with conventional therapies presents opportunities for enhanced treatment efficacy. Specifically, blocking EV-pIgR with neutralizing antibodies, when integrated with conventional hepatocellular carcinoma therapies such as sorafenib or other therapeutic agents, or a dIgA-targeting approach combined with immune checkpoint inhibitors, may enhance treatment efficacy. This review also addresses current challenges and future directions in pIgR-targeted cancer therapy, emphasizing the need for a deeper understanding of pIgR's regulatory mechanisms. These insights reveal that pIgR is an emerging therapeutic target with significant potential for the development of novel cancer treatment strategies.
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Affiliation(s)
- Shaoju Qian
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Yeqing He
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Ruixue Li
- Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Panpan Sun
- Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Xingyi Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Lin Pan
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Zhishan Xu
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Zhiwei Feng
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Rong Lian
- Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China.
| | - Lili Yu
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China.
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China.
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China.
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Miquel M, Zhang S, Pilarsky C. Pre-clinical Models of Metastasis in Pancreatic Cancer. Front Cell Dev Biol 2021; 9:748631. [PMID: 34778259 PMCID: PMC8578999 DOI: 10.3389/fcell.2021.748631] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 09/20/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a hostile solid malignancy coupled with an extremely high mortality rate. Metastatic disease is already found in most patients at the time of diagnosis, resulting in a 5-year survival rate below 5%. Improved comprehension of the mechanisms leading to metastasis is pivotal for the development of new targeted therapies. A key field to be improved are modeling strategies applied in assessing cancer progression, since traditional platforms fail in recapitulating the complexity of PDAC. Consequently, there is a compelling demand for new preclinical models that mirror tumor progression incorporating the pressure of the immune system, tumor microenvironment, as well as molecular aspects of PDAC. We suggest the incorporation of 3D organoids derived from genetically engineered mouse models or patients as promising new tools capable to transform PDAC pre-clinical modeling and access new frontiers in personalized medicine.
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Affiliation(s)
- Maria Miquel
- Department of Surgery, University Hospital, Erlangen, Germany
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Shuman Zhang
- Department of Surgery, University Hospital, Erlangen, Germany
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Christian Pilarsky
- Department of Surgery, University Hospital, Erlangen, Germany
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Abstract
Pancreatic cancer is the third leading cause of cancer death in the USA, and pancreatic ductal adenocarcinoma (PDA) constitutes 85% of pancreatic cancer diagnoses. PDA frequently metastasizes to the peritoneum, but effective treatment of peritoneal metastasis remains a clinical challenge. Despite this unmet need, understanding of the biological mechanisms that contribute to development and progression of PDA peritoneal metastasis is sparse. By contrast, a vast number of studies have investigated mechanisms of peritoneal metastasis in ovarian and gastric cancers. Here, we contrast similarities and differences between peritoneal metastasis in PDA as compared with those in gastric and ovarian cancer by outlining molecular mediators involved in each step of the peritoneal metastasis cascade. This review aims to provide mechanistic insights that could be translated into effective targeted therapies for patients with peritoneal metastasis from PDA.
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Huang X, Qian Y, Wu H, Xie X, Zhou Q, Wang Y, Kuang W, Shen L, Li K, Su J, Shen L, Chen X. Aberrant expression of osteopontin and E-cadherin indicates radiation resistance and poor prognosis for patients with cervical carcinoma. J Histochem Cytochem 2014; 63:88-98. [PMID: 25380749 DOI: 10.1369/0022155414561329] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group (p<0.001). These patients also had a lower 5-year PFS rate (p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001).
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Affiliation(s)
- Xinqiong Huang
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Yujie Qian
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Hainan Wu
- Department of Clinical Medicine, the NCO School of the Border Control Force Yunnan Province, P.R. China (HW)
| | - Xiaoxue Xie
- Department of Radiation Oncology, Hunan Provincial Tumal Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Hunan Province, P.R. China (XX)
| | - Qin Zhou
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Ying Wang
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Weilu Kuang
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Lin Shen
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL),Xiangya of medicine, Central South University, Hunan Province, P.R. China (LS)
| | - Kai Li
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL)
| | - Juan Su
- Department of Dermatology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (XC, JS)
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (LS, XH, YQ, QZ, YW, WK, KL),Xiangya of medicine, Central South University, Hunan Province, P.R. China (LS)
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Hunan Province, P.R. China (XC, JS)
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CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells. Exp Cell Res 2013; 321:209-18. [PMID: 24384474 DOI: 10.1016/j.yexcr.2013.12.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 12/17/2013] [Accepted: 12/18/2013] [Indexed: 11/20/2022]
Abstract
The prognosis of pancreatic cancer is dismal due to the frequent metastasis and invasion to surrounding organs. Numerous molecules are involved in the malignant behavior of pancreatic cancer cells, but the entire process remains unclear. Several reports have suggested that CUB-domain containing protein-1 (CDCP1) is highly expressed in pancreatic cancer, but its impact on the invasive growth and the upstream regulator remain elusive. To clarify the role of CDCP1 in pancreatic cancer, we here examined the effects of CDCP1 knockdown on the cell behaviors of pancreatic cancer cells. Knockdown of CDCP1 expression in Panc-1 resulted in reduced cellular migration accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin. Knockdown of CDCP1 attenuated the spheroid formation and resistance against gemcitabine, which are some of the cancer stem cell-related phenotypes. Bone morphogenetic protein 4 (BMP4) was found to induce CDCP1 expression via the extracellular signal regulated kinase pathway, suggesting that CDCP1 has a substantial role in the BMP4-induced epithelial-mesenchymal transition. These results indicate that CDCP1 represses the epithelial phenotype of pancreatic cancer cells.
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Hamada S, Satoh K, Masamune A, Shimosegawa T. Regulators of epithelial mesenchymal transition in pancreatic cancer. Front Physiol 2012; 3:254. [PMID: 22934011 PMCID: PMC3429031 DOI: 10.3389/fphys.2012.00254] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Accepted: 06/19/2012] [Indexed: 12/21/2022] Open
Abstract
Pancreatic cancer is a leading cause of cancer-related death due to its invasive nature. Despite the improvement of diagnostic strategy, early diagnosis of pancreatic cancer is still challenging. Surgical resection is the only curative therapy, while vast majority of patients are not eligible for this therapeutic option. Complex biological processes are involved in the establishment of invasion and metastasis of pancreatic cancer and epithelial-mesenchymal transition (EMT) has been reported to play crucial role. EMT is part of the normal developmental processes which mobilizes epithelial cells and yields mesenchymal phenotype. Deregulation of EMT inducing molecules in pancreatic cancer is reported, such as multiple cytokines, growth factors and downstream transcriptional factors. In addition to these molecules, non-coding RNA including miRNA also contributes to EMT. EMT of cancer cell also correlates with cancer stem cell (CSC) properties such as chemoresistance or tumorigenicity, therefore these upstream regulators of EMT could be attractive therapeutic targets and several candidates are examined for clinical application. This review summarizes recent advances in this field, focusing the regulatory molecules of EMT and their downstream targets. Further understanding and research advances will clarify the cryptic mechanism of cancer metastasis and delineate novel therapeutic targets.
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Affiliation(s)
- Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi, Japan
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Orlichenko L, Weller SG, Cao H, Krueger EW, Awoniyi M, Beznoussenko G, Buccione R, McNiven MA. Caveolae mediate growth factor-induced disassembly of adherens junctions to support tumor cell dissociation. Mol Biol Cell 2009; 20:4140-52. [PMID: 19641024 DOI: 10.1091/mbc.e08-10-1043] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Remodeling of cell-cell contacts through the internalization of adherens junction proteins is an important event during both normal development and the process of tumor cell metastasis. Here we show that the integrity of tumor cell-cell contacts is disrupted after epidermal growth factor (EGF) stimulation through caveolae-mediated endocytosis of the adherens junction protein E-cadherin. Caveolin-1 and E-cadherin closely associated at cell borders and in internalized structures upon stimulation with EGF. Furthermore, preventing caveolae assembly through reduction of caveolin-1 protein or expression of a caveolin-1 tyrosine phospho-mutant resulted in the accumulation of E-cadherin at cell borders and the formation of tightly adherent cells. Most striking was the fact that exogenous expression of caveolin-1 in tumor cells that contain tight, well-defined, borders resulted in a dramatic dispersal of these cells. Together, these findings provide new insights into how cells might disassemble cell-cell contacts to help mediate the remodeling of adherens junctions, and tumor cell metastasis and invasion.
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Affiliation(s)
- Lidiya Orlichenko
- Mayo Clinic, Department of Biochemistry and Molecular Biology and the Miles and Shirley Fiterman Center for Digestive Diseases, Rochester, MN 55905, USA
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Yalta T, Atay L, Atalay F, Çaydere M, Gonultas M, Ustun H. E-Cadherin Expression in Endometrial Malignancies: Comparison between Endometrioid and Non-Endometrioid Carcinomas. J Int Med Res 2009; 37:163-8. [DOI: 10.1177/147323000903700119] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
This study examined the frequency of E-cadherin expression in endometrial biopsy or hysterectomy specimens from patients diagnosed with endometrial adenocarcinoma and in normal endometrial tissue specimens. E-cadherin expression was detected by immunohistochemistry using monoclonal antibody to E-cadherin. Specimens were classified as positive when ≥ 5% of the tumour cells showed staining for E-cadherin, irrespective of the pattern of staining. Twenty-three endometrioid carcinomas and nine non-endometrioid (four papillary serous and five clear cell) carcinomas were studied, along with 10 normal endometrial tissue specimens as controls. E-cadherin expression was significantly less frequent in non-endometrioid carcinomas compared with endometrioid carcinomas and controls. There was no statistically significant difference in the frequency of E-cadherin expression between endometrioid carcinomas and controls. In conclusion, this study demonstrated that uterine non-endometrioid (papillary serous and clear cell) carcinomas were less likely to express E-cadherin compared with endometrioid carcinomas and normal endometrial tissue. This may help to explain the more aggressive behaviour of non-endometrioid carcinomas.
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Affiliation(s)
- T Yalta
- Pathology Department, Sivas State Hospital, Sivas, Turkey
| | - L Atay
- Pathology Department, Ankara Training and Research Hospital, Ankara, Turkey
| | - F Atalay
- Pathology Department, Ankara Training and Research Hospital, Ankara, Turkey
| | - M Çaydere
- Pathology Department, Ankara Training and Research Hospital, Ankara, Turkey
| | - M Gonultas
- Pathology Department, Ankara Training and Research Hospital, Ankara, Turkey
| | - H Ustun
- Pathology Department, Ankara Training and Research Hospital, Ankara, Turkey
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Chunthapong J, Seftor EA, Khalkhali-Ellis Z, Seftor REB, Amir S, Lubaroff DM, Heidger PM, Hendrix MJC. Dual roles of E-cadherin in prostate cancer invasion. J Cell Biochem 2004; 91:649-61. [PMID: 14991757 DOI: 10.1002/jcb.20032] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The role(s) of E-cadherin in tumor progression, invasion, and metastasis remains somewhat enigmatic. In order to investigate various aspects of E-cadherin biological activity, particularly in prostate cancer progression, our laboratory cloned unique subpopulations of the heterogeneous DU145 human prostatic carcinoma cell line and characterized their distinct biological functions. The data revealed that the highly invasive, fibroblastic-like subpopulation of DU145 cells (designated DU145-F) expressed less than 0.1-fold of E-cadherin protein when compared to the parental DU145 or the poorly invasive DU145 cells (designated DU145-E). Experimental disruption of E-cadherin function stimulated migration and invasion of DU145-E and other E-cadherin-positive prostate cancer cell lines, but did not affect the fibroblastic-like DU145-F subpopulation. Within the medium of parental DU145 cells, the presence of an 80 kDa E-cadherin fragment was detected. Subsequent functional analyses revealed the stimulatory effect of this fragment on the migratory and invasive capability of E-cadherin-positive cells. These results suggest that E-cadherin plays an important role in regulating the invasive potential of prostate cancer cells through an unique paracrine mechanism.
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Affiliation(s)
- Jirapat Chunthapong
- Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242-1109, USA
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Li YJ, Ji XR. Relationship between expression of E-cadherin-catenin complex and clinicopathologic characteristics of pancreatic cancer. World J Gastroenterol 2003; 9:368-72. [PMID: 12532469 PMCID: PMC4611349 DOI: 10.3748/wjg.v9.i2.368] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression of E-cadherin and alpha-catenin and beta-catenin in pancreatic carcinoma and its relationship with the clinicopathologic characteristics, and clarify the mechanism of invasion and metastasis of pancreatic cancer.
METHODS: The expression of E-cadherin and alpha-, beta-catenin was examined in 47 cases of infiltrative ductal adenocarcinoma of pancreas and 12 adult normal pancreatic tissues by immunohistochemical technique.
RESULTS: The immunoreactivity of E-cadherin and alpha-, beta-catenin was expressed by normal ductal and acinar cells with strong membranous staining at the intercellular border in 12 cases of adult normal pancreatic tissues. Abnormal expression of E-cadherin and alpha-, beta-catenin in 47 pancreatic carcinoma tissues was demonstrated in 53.2%, 61.7% and 68.1%, respectively. Both abnormal expression of E-cadherin and alpha-catenin significantly correlated with differentiation, lymph node and liver metastases (P < 0.05, respectively), whereas aberrant beta-catenin expression only correlated with lymph node and liver metastases (P < 0.001). Abnormal E-cadherin and alpha-, beta-catenin expression was not associated with tumor size, invasion and survival time of patients (P > 0.05, all).
CONCLUSION: Pancreatic cancer likely occurs in case of E-cadherin-catenin complex genes mutations or deletions and abnormal expression of proteins, which significantly correlate with the biologic character of the tumor and lymph node and liver metastases. It is suggested that the abnormal E-cadherin-catenin complex expression plays an important role in the development and progression of tumor, and thus may become a new marker in pancreatic cancer metastasis.
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Affiliation(s)
- Yu-Jun Li
- Department of Pathology, the Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Rd, Qingdao 266003, China.
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Akutagawa N, Nishikawa A, Iwasaki M, Fujimoto T, Teramoto M, Kitajima Y, Endo T, Shibuya M, Kudo R. Expression of vascular endothelial growth factor and E-cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model. Jpn J Cancer Res 2002; 93:644-51. [PMID: 12079512 PMCID: PMC5927051 DOI: 10.1111/j.1349-7006.2002.tb01302.x] [Citation(s) in RCA: 19] [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: 01/06/2023] Open
Abstract
Ascites formation and peritoneal dissemination are critical problems in patients with advanced ovarian cancer. Vascular endothelial growth factor (VEGF), also known as angiogenic growth factor, is a potent mediator of peritoneal fluid accumulation and angiogenesis of tumors. E-Cadherin is an adhesion molecule that is important for cell-to-cell interaction. To elucidate the molecular mechanism of ascites formation and peritoneal dissemination of ovarian cancer, we examined the expression of VEGF and E-cadherin in different ovarian cancer cell lines and utilized nude mice to compare the biological characteristics of ovarian cancer cells. Three human ovarian cancer cell lines (AMOC-2, HNOA and HTBOA) were used in this study. Expression of genes was analyzed by northern blotting and RT-PCR methods. AMOC-2 expressed E-cadherin, but not VEGF. HNOA expressed VEGF without E-cadherin expression. HTBOA expressed both VEGF and E-cadherin. Each human ovarian cancer model revealed a specific feature. The AMOC-2 mouse had a single large peritoneal tumor without ascites or remarkable peritoneal dissemination. HTBOA and HNOA mice had bloody ascites and marked peritoneal dissemination. Introduction of VEGF antisense into HTBOA cells could inhibit the ascites formation. It is suggested that VEGF is important for the ascites formation via the increased vascular permeability effect. The deregulation of E-cadherin expression might be involved in the peritoneal dissemination. These molecules are important for the formation of specific features of advanced ovarian cancer. Ovarian cancer cell lines that had different gene expression patterns produced nude mouse human ovarian cancer models with different characteristics.
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Affiliation(s)
- Noriyuki Akutagawa
- Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Chuo-ku, Sapporo 060-8543
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Yachida S, Fukushima N, Sakamoto M, Matsuno Y, Kosuge T, Hirohashi S. Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer. Br J Surg 2002; 89:573-8. [PMID: 11972546 DOI: 10.1046/j.1365-2168.2002.02061.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. METHODS Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. RESULTS One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.
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Affiliation(s)
- S Yachida
- Clinical Laboratory Division and Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital and Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
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Lindner V, Booth C, Prudovsky I, Small D, Maciag T, Liaw L. Members of the Jagged/Notch gene families are expressed in injured arteries and regulate cell phenotype via alterations in cell matrix and cell-cell interaction. THE AMERICAN JOURNAL OF PATHOLOGY 2001; 159:875-83. [PMID: 11549580 PMCID: PMC1850458 DOI: 10.1016/s0002-9440(10)61763-4] [Citation(s) in RCA: 145] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The Jagged/Notch signaling pathways control cell fate determination and differentiation, and their dysfunction is associated with human pathologies involving cardiovascular abnormalities. To determine the presence of these genes during vascular response to injury, we analyzed expression of Jagged1, Jagged2, and Notch1 through 4 after balloon catheter denudation of the rat carotid artery. Although low levels of Jagged1, Jagged2, and constitutive expression of Notch1 were seen in uninjured endothelium, expression of all was significantly increased in injured vascular cells. High Jagged1 expression was restricted to the regenerating endothelial wound edge, whereas Notch transcripts were abundant in endothelial and smooth muscle cells. To understand the basis for Jagged/Notch control of cellular phenotype, we studied an in vitro model of NIH3T3 cells transfected with a secreted form of the extracellular domain of Jagged1. We report that the soluble Jagged1 protein caused decreased cell-matrix adhesion and cell migration defects. Cadherin-mediated intercellular junctions as well as focal adhesions were modified in soluble Jagged1 transfectants, demonstrating that cell-cell contacts and adhesion plaques may be targets of Jagged/Notch activity. We suggest that Jagged regulation of cell-cell and cell-matrix interactions may contribute to the control of cell migration in situations of tissue remodeling in vivo.
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Affiliation(s)
- V Lindner
- Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA
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