Abstract 1414: Lysophosphatidic acid-induced Cyr61 is associated with prostate cancer progression

Abstract

Abstract Lysophosphatidic acid (LPA) is a serum phospholipid that has been associated with progression in several types of cancer. Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. We have reported that Cyr61 expression in benign prostate cells is regulated by LPA (Endocrinology 2004). Furthermore that Cyr61 expression is significantly up-regulated in prostate cancer (PCa) and that the expression levels correlate with Gleason score (J Urol 2010). The aim of this study was to determine if LPA-induced Cyr61 up-regulation is associated with PCa progression. BPH1 was utilized as a benign prostate cell line and PC3 as a PCa cell line. In real-time PCR of untreated BPH1 and PC3 cells, Cyr61 expression ratios to TBP were 0.5 and 5.1, and these ratios after 2 hours of 1uM LPA under serum-free medium treatment were 1.8 and 44.3, respectively. These results indicated that the Cyr61 expression levels and their increase by LPA stimulation were higher in PCa cells than in benign prostate cells. To examine whether LPA promotes cell invasion, Matrigel invasion assays were performed for 72 hours with or without 1uM of LPA in the lower chamber. LPA stimulation increased the invaded cell number from 0.3±0.5 to 12.6±2.5 (p<0.001) in BPH1 cells and from 31.9±20.9 to 55.2±14.8 (p=0.005) in PC3 cells. These results indicate that LPA promotes cell invasion in both benign prostate and PCa cells. To examine whether LPA-induced Cyr61 is associated with cell invasion, the Cyr61 was knocked down by siRNA in PC3 cells. Invaded cell numbers were changed by 48 hours of LPA stimulation after scramble siRNA from 2.2±1.3 to 12.3±10.2 (p=0.002) and after Cyr61 targeting siRNA from 1.8±2.6 to 2.7±2.7 (p=0.235), respectively, revealing that Cyr61 down-regulation suppresses LPA induced cell invasion. To investigate the association between Cyr61 up-regulation and prostate carcinogenesis, Cyr61 over-expressing BPH1 cells (BPH1-Cyr61) were established and their cell proliferation was compared with vector only transfected BPH1 cells (BPH1-mock) by MTS assays. The cell proliferation ratio of BPH1-mock and BPH1-Cyr61 cells after 48 hours of incubation in serum-free medium was 1.24±0.05 and 1.40±0.02 (p=0.043), respectively, indicating that Cyr61 over-expression promoted cell proliferation of BPH1 in vitro. In conclusion, LPA induced Cyr61 up-regulation was suggested to be associated with PCa progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1414. doi:10.1158/1538-7445.AM2011-1414