This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Long, H. Articles by Gabig, T. G. Search for Related Content PubMed PubMed Citation Articles by Long, H. Articles by Gabig, T. G.

Expression of Clostridium Perfringens Enterotoxin Receptors Claudin-3 and Claudin-4 in Prostate Cancer Epithelium

Departments of Medicine [H. L., C. D. C., T. G. G.], Pediatrics [W-H. L.], and Pathology [O. W. C.], Indiana University School of Medicine, Indianapolis, Indiana 46202

The mRNA for Rvp.1 (rat ventral prostate) increases in abundance before gland involution after androgen deprivation. Rvp.1 is homologous to CPE-R, the high-affinity intestinal epithelial receptor for Clostridium perfringens enterotoxin (CPE), and is sufficient to mediate CPE binding and trigger subsequent toxin-mediated cytolysis. Rvp.1 (claudin-3) and CPE-R (claudin-4) are members of a larger family of transmembrane tissue-specific claudin proteins that are essential components of intercellular tight junction structures regulating paracellular ion flux. However, claudin-3 and claudin-4 are the only family members capable of mediating CPE binding and cytolysis. The present study was designed to study the expression of claudin-3 and claudin-4 in human prostate tissue as potential targets for CPE toxin-mediated therapy for prostate cancer. On human multiple-tissue Northern blot analysis, mRNAs for both claudin-3 and claudin-4 were expressed at high levels in prostate tissue. In normal prostate tissue, expression of claudin-3 was localized exclusively within acinar epithelial cells by in situ mRNA hybridization. Compared with expression within prostate epithelial cells in surrounding normal glandular tissue, expression of claudin-3 mRNA remained high in the epithelium of prostate adenocarcinoma (10 of 10) and prostatic intraepithelial neoplasia (five of five). Prostate adenocarcinoma cells metastatic to bone were obtained from a patient with disease progression during antiandrogen therapy. These metastatic cells were prostate-specific antigen-positive by immunohistochemical staining and also expressed functional CPE receptors as measured by sensitivity to CPE-induced cell lysis. The persistent high level of claudin-3 expression in prostate adenocarcinoma and functional cytotoxicity of CPE in metastatic androgen-independent prostate adenocarcinoma suggests a new potential therapeutic strategy for prostate cancer.

This article has been cited by other articles:

				R. Saeki, M. Kondoh, H. Kakutani, S.-i. Tsunoda, Y. Mochizuki, T. Hamakubo, Y. Tsutsumi, Y. Horiguchi, and K. Yagi A Novel Tumor-Targeted Therapy Using a Claudin-4-Targeting Molecule Mol. Pharmacol., October 1, 2009; 76(4): 918 - 926. [Abstract] [Full Text] [PDF]

				X. Yuan, X. Lin, G. Manorek, I. Kanatani, L. H. Cheung, M. G. Rosenblum, and S. B. Howell Recombinant CPE fused to tumor necrosis factor targets human ovarian cancer cells expressing the claudin-3 and claudin-4 receptors Mol. Cancer Ther., July 1, 2009; 8(7): 1906 - 1915. [Abstract] [Full Text] [PDF]

				Y.-H. Huang, Y. Bao, W. Peng, M. Goldberg, K. Love, D. A. Bumcrot, G. Cole, R. Langer, D. G. Anderson, and J. A. Sawicki Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis PNAS, March 3, 2009; 106(9): 3426 - 3430. [Abstract] [Full Text] [PDF]

				Y.-C. Chao, S.-H. Pan, S.-C. Yang, S.-L. Yu, T.-F. Che, C.-W. Lin, M.-S. Tsai, G.-C. Chang, C.-H. Wu, Y.-Y. Wu, et al. Claudin-1 Is a Metastasis Suppressor and Correlates with Clinical Outcome in Lung Adenocarcinoma Am. J. Respir. Crit. Care Med., January 15, 2009; 179(2): 123 - 133. [Abstract] [Full Text] [PDF]

				S. L. Kominsky, B. Tyler, J. Sosnowski, K. Brady, M. Doucet, D. Nell, J. G. Smedley III, B. McClane, H. Brem, and S. Sukumar Clostridium perfringens Enterotoxin as a Novel-Targeted Therapeutic for Brain Metastasis Cancer Res., September 1, 2007; 67(17): 7977 - 7982. [Abstract] [Full Text] [PDF]

				M. Lioni, P. Brafford, C. Andl, A. Rustgi, W. El-Deiry, M. Herlyn, and K. S.M. Smalley Dysregulation of Claudin-7 Leads to Loss of E-Cadherin Expression and the Increased Invasion of Esophageal Squamous Cell Carcinoma Cells Am. J. Pathol., February 1, 2007; 170(2): 709 - 721. [Abstract] [Full Text] [PDF]

				J. J. Stewart, J. T. White, X. Yan, S. Collins, C. W. Drescher, N. D. Urban, L. Hood, and B. Lin Proteins Associated with Cisplatin Resistance in Ovarian Cancer Cells Identified by Quantitative Proteomic Technology and Integrated with mRNA Expression Levels Mol. Cell. Proteomics, March 1, 2006; 5(3): 433 - 443. [Abstract] [Full Text] [PDF]

				Y Soini, V Kinnula, K Kahlos, and P Paakko Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. J. Clin. Pathol., March 1, 2006; 59(3): 250 - 254. [Abstract] [Full Text] [PDF]

				C. Ebihara, M. Kondoh, N. Hasuike, M. Harada, H. Mizuguchi, Y. Horiguchi, M. Fujii, and Y. Watanabe Preparation of a Claudin-Targeting Molecule Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 255 - 260. [Abstract] [Full Text] [PDF]

				P. J. Morin Claudin Proteins in Human Cancer: Promising New Targets for Diagnosis and Therapy Cancer Res., November 1, 2005; 65(21): 9603 - 9606. [Abstract] [Full Text] [PDF]

				R. Agarwal, T. D'Souza, and P. J. Morin Claudin-3 and Claudin-4 Expression in Ovarian Epithelial Cells Enhances Invasion and Is Associated with Increased Matrix Metalloproteinase-2 Activity Cancer Res., August 15, 2005; 65(16): 7378 - 7385. [Abstract] [Full Text] [PDF]

				A. D. Santin, S. Cane, S. Bellone, M. Palmieri, E. R. Siegel, M. Thomas, J. J. Roman, A. Burnett, M. J. Cannon, and S. Pecorelli Treatment of Chemotherapy-Resistant Human Ovarian Cancer Xenografts in C.B-17/SCID Mice by Intraperitoneal Administration of Clostridium perfringens Enterotoxin Cancer Res., May 15, 2005; 65(10): 4334 - 4342. [Abstract] [Full Text] [PDF]

				K. Hibbs, K. M. Skubitz, S. E. Pambuccian, R. C. Casey, K. M. Burleson, T. R. Oegema Jr, J. J. Thiele, S. M. Grindle, R. L. Bliss, and A. P.N. Skubitz Differential Gene Expression in Ovarian Carcinoma: Identification of Potential Biomarkers Am. J. Pathol., August 1, 2004; 165(2): 397 - 414. [Abstract] [Full Text] [PDF]

				S. L. Kominsky, M. Vali, D. Korz, T. G. Gabig, S. A. Weitzman, P. Argani, and S. Sukumar Clostridium perfringens Enterotoxin Elicits Rapid and Specific Cytolysis of Breast Carcinoma Cells Mediated through Tight Junction Proteins Claudin 3 and 4 Am. J. Pathol., May 1, 2004; 164(5): 1627 - 1633. [Abstract] [Full Text] [PDF]

				P. Michl, C. Barth, M. Buchholz, M. M. Lerch, M. Rolke, K.-H. Holzmann, A. Menke, H. Fensterer, K. Giehl, M. Lohr, et al. Claudin-4 Expression Decreases Invasiveness and Metastatic Potential of Pancreatic Cancer Cancer Res., October 1, 2003; 63(19): 6265 - 6271. [Abstract] [Full Text] [PDF]

				L. B. A. Rangel, R. Agarwal, T. D'Souza, E. S. Pizer, P. L. Alo, W. D. Lancaster, L. Gregoire, D. R. Schwartz, K. R. Cho, and P. J. Morin Tight Junction Proteins Claudin-3 and Claudin-4 Are Frequently Overexpressed in Ovarian Cancer but Not in Ovarian Cystadenomas Clin. Cancer Res., July 1, 2003; 9(7): 2567 - 2575. [Abstract] [Full Text] [PDF]

				A. Riesewijk, J. Martin, R. van Os, J. A. Horcajadas, J. Polman, A. Pellicer, S. Mosselman, and C. Simon Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology Mol. Hum. Reprod., May 1, 2003; 9(5): 253 - 264. [Abstract] [Full Text] [PDF]