Caveolin-1 and -2 regulate cell motility in castration-resistant prostate cancer
Received 7 May 2018
Accepted for publication 16 July 2018
Published 3 October 2018 Volume 2018:10 Pages 135—144
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Jan Colli
Toyoharu Kamibeppu, Koji Yamasaki, Kozue Nakahara, Takahiro Nagai, Naoki Terada, Hiromasa Tsukino, Shoichiro Mukai, Toshiyuki Kamoto
Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake, Japan
Background: Caveolin (Cav)-1 and Cav-2 are cell membrane proteins, which are structural proteins of caveolae and are reported to be positive regulators of cell survival and metastasis in prostate cancer (PC). In a previous study, we reported that elevated levels of Cav-1 and Cav-2 were significantly associated with PC progression. However, their functions in PC have not yet been clarified. In this study, we examined the function of Cav-1 and Cav-2 in PC cell invasiveness and motility.
Materials and methods: We introduced Cav-1- and Cav-2-specific small interfering into PC3 cells to knock-down (KD) both molecules. We also performed cell proliferation assay, wound healing assay, migration assay, and invasion assay using PC3 cells and compared the results between Cav-1-KD, Cav-2-KD, and negative control PC3 cells. In addition, we performed real-time quantitative PCR (RT-qPCR) and RT2 Profiler PCR Array analysis to identify factors influencing migration.
Results: We observed no significant difference in the proliferative and invasive activities of Cav-1-KD and Cav-2-KD PC3 cells; however, the cell motility was significantly decreased compared with negative control PC3 cells. RT-qPCR revealed that the expression of vimentin and N-cadherin was downregulated in Cav-1-KD PC3 cells. In addition, PCR array revealed a decreased expression of MGAT5, MMP13, and MYCL in Cav-1-KD PC3 and ETV4, FGFR4, and SRC in Cav-2-KD PC3.
Conclusion: Cav-1 and Cav-2 may positively contribute to the upregulation of castration-resistant PC cell migration. Cav-induced regulation of several molecules including vimentin, N-cadherin, MGAT5, MMP13, MYCL, ETV4, FGFR4, and SRC may have an important role in PC3 cell motility. However, further examination will be required.
Keywords: caveolin-1, caveolin-2, CRPC, cell motility
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