Abstract B67: Matriptase is involved in COX-2 signaling-induced prostate cancer cell invasion

Abstract

Abstract Chronic inflammation plays an important role in the early development and progression of cancer. Cyclooxygenases-2 (COX-2) is a key rate-limiting enzyme which regulates of inflammation-producing prostaglandins. Several studies have shown that COX-2 is found with overexpression in human cancers (colon, breast, lung, prostate cancers, etc), and implicated in cancer cell invasion. Moreover, high COX-2 expression has been correlated with prostate cancer metastasis. However, the molecular mechanism that COX-2 promotes prostate cancer cell invasion is still unclear. In this study, we established a PC-3 cell invasion progression model (parental and M2I2 PC-3 cells) and found out that several inflammation-associated proteins, COX-2, p-JNK and IL-1β were up-regulated in M2I2 PC-3 cells. Therefore, we purposed that if COX-2 signaling plays a role in prostate cancer cell invasion and the involvement of matriptase in COX-2 signaling-induced cancer cell invasion. The results showed that COX-2 inhibitors (celebrex and sulindac sulfide) could suppress prostate cancer PC3 cell invasion and inhibited matriptase expression and activation. A COX-2 product PGE2 could induce matriptase activation and prostate cancer cell invasion. COX-2 overexpression also could up-regulate matriptase and enhance the cancer cell invasion, while COX-2 silencing antagonized both matriptase activation and cell invasion. Thus, our results indicate that COX-2 signaling can promote prostate cancer cell invasion, at least in part via up-regulating matriptase. Citation Format: Chun-Jung Ko, Ying-Chieh Lu, Pee-Fang Lai, Pei-Wen Hsiao, Ming-Shyue Lee. Matriptase is involved in COX-2 signaling-induced prostate cancer cell invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B67.