ECTS Abstracts (2015) 1 CABSOC4.3

FZD5 mediates the anti-proliferative, but not the pro-apoptotic effects of WNT5A on prostate cancer cells

Stefanie Thiele1, Andy Göbel1, Sandra Hippauf1, Tilman D Rachner1, Franz Jakob2, Martina Rauner1 & Lorenz C Hofbauer1,3

1Technical University, Dresden, Dresden, Germany; 2University of Würzburg, Würzburg, Germany; 3Center for Regenerative Therapies Dresden, Dresden, Germany.

Wnt proteins and their cognate receptors play a significant role in malignant diseases, in particular in PCa. Previously, we could show that WNT5A inhibits PCa cell proliferation and induces apoptosis in vitro, leading to reduced PCa growth in vivo. However, the involved receptors remain unknown. Here, we determined which receptors mediate the WNT5A-induced effects on PCa cells. The expression profile of 12 different Wnt receptors was analysed in three human (PC3, C42B, MDA-PCa-2b) and two mouse (RM1, TRAMP-C2) PCa cell lines. Frizzled (FZD) 10 and FZD9 showed the lowest expression levels in the PCa cell lines, while FZD1; FZD6, and Ryk were highly expressed. To determine which receptors mediate the anti-proliferative and pro-apoptotic effects of WNT5A in PCa, we knocked down FZD5 and receptor tyrosin-like orphan receptor (ROR) 2 with specific siRNA in PC3 cells 24 h before the induction of WNT5A overexpression. After knock-down of ROR2, WNT5A was still able to suppress proliferation by 31%. However, FZD5 knock-down completely reversed the suppressive effect of WNT5A on proliferation. The knock-down of FZD5 and ROR2 itself did not change PCa cell proliferation. Interestingly, the increase of apoptosis after WNT5A overexpression could not been reversed by neither knock-down of FZD5 or ROR2, suggesting another receptor involved in this process. Of note, knock-down of FZD5 even further increased apoptosis after WNT5A overexpression. A cDNA array containing samples from 9 healthy and 39 patients with prostate cancer was evaluated for WNT5A, FZD5, and ROR2 expression. WNT5A, FZD5, and ROR2 mRNA expression was significantly higher in the prostate cancer samples compared with healthy controls (P<0.001). However, only FZD5 expression correlated highly positively with WNT5A expression (r2=0.8801, P<0.001). These data suggest that FZD5, but not ROR2, mediates the anti-proliferative effects of WNT5A on prostate cancer cells.

Disclosure: The authors declared no competing interests.

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