Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium

• Published in: Cancer research (Chicago, Ill.) Ill.), 2001-11, Vol.61 (21), p.7878-7881
• Main Authors: HAIYAN LONG, CREAN, Colin D, LEE, Wei-Hua, CUMMINGS, O. William, GABIG, Theodore G
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - secondary; Androgens - physiology; Animals; Biological and medical sciences; Bone Marrow Neoplasms - drug therapy; Bone Marrow Neoplasms - metabolism; Bone Marrow Neoplasms - secondary; Cercopithecus aethiops; Claudin-3; Claudin-4; Clostridium perfringens - genetics; Clostridium perfringens - metabolism; Enterotoxins - metabolism; Enterotoxins - toxicity; Epithelial Cells - metabolism; Epithelial Cells - pathology; Humans; Male; Medical sciences; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - metabolism; Nephrology. Urinary tract diseases; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumors of the urinary system; Urinary tract. Prostate gland; Vero Cells
• ISSN: 0008-5472; 1538-7445

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.