The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells

• Published in: Urology (Ridgewood, N.J.) N.J.), 2017-03, Vol.101, p.169.e7-169.e13
• Main Authors: Shintani, Terumichi, Kusuhara, Yoshito, Daizumoto, Kei, Dondoo, Tsogt-Ochir, Yamamoto, Hiroki, Mori, Hidehisa, Fukawa, Tomoya, Nakatsuji, Hiroyoshi, Fukumori, Tomoharu, Takahashi, Masayuki, Kanayama, Hiroomi
• Format: Article
• Language: English
• Subjects: Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2016.12.006

Objectives To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. Methods We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. Results MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P