The involvement of altered corticotropin releasing factor receptor 2 expression in prostate cancer due to alteration of anti-angiogenic signaling pathways

BACKGROUND. Expression of urocortin (Ucn) in the human benign prostate and prostate cancer has been reported recently. Ucn binds and activates corticotropin releasing factor (CRF) receptor 1 (CRFR1) and 2 (CRFR2). Activation of CRFR2 has been shown to inhibit tumor growth by regulation of proliferation and apoptosis as well as suppression of vascularization. However, there is no report demonstrating expression profile of CRFR2 in normal prostate versus prostate cancer. METHODS. CRFR2 mRNA expression was assessed in human normal prostate and prostate cancer by reverse transcriptase PCR. CRFR2 expression on protein level has been performed using double staining immunofluorescence (IF) of tissue microarrays of 32 cases of prostatic adenocarcioma with corresponding normal tissues. Confocal microscopy was carried out to visualize the immunostaining. RESULTS. PCR of normal prostate lysates exhibited specific signals for CRFR2 mRNA. However PCR of lysates of prostate cancer exhibited no signal for CRFR2 mRNA. IF study exhibited that smooth muscle components of the stroma and endothelial cells of blood vessels express an extensive staining for CRFR2. In a lesser extend vascular smooth muscle cells expressed CRFR2. The tumoral neovascular system and stroma exhibited no immunopositivity for CRFR2. CONCLUSIONS. The present study demonstrates for the first time that human benign prostate tissue and prostate cancer specimen differentially express CRFR2. While Ucn expression in prostate cancer has been shown to be identical to non-malignant prostate tissues, we hypothesize that expression loss of CRFR2 in prostate cancer and its neovascularization contributes to prostate tumorigenesis, progression, and neoangiogenesis.