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

Shintani, Terumichi ; Kusuhara, Yoshito ; et al.

In: Urology, Jg. 101 (2016-12-21)

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Titel:	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
Autor/in / Beteiligte Person:	Shintani, Terumichi ; Kusuhara, Yoshito ; Daizumoto, Kei ; Dondoo, Tsogt-Ochir ; Yamamoto, Hiroki ; Mori, Hidehisa ; Fukawa, Tomoya ; Nakatsuji, Hiroyoshi ; Fukumori, Tomoharu ; Takahashi, Masayuki ; Kanayama, Hiroomi
Link:	View record in National Diet Library Digital Collections (Volltext) E-Journal im Bestand der UB Hagen?
Zeitschrift:	Urology, Jg. 101 (2016-12-21)
Veröffentlichung:	2016
Medientyp:	Hochschulschrift
ISSN:	0090-4295 (print)
DOI:	10.1016/j.urology.2016.12.006
Schlagwort:	HGF MET Cabozantinib MMP Bladder cancer HGF-MET Matrix Metalloproteinase 1
Sonstiges:	Nachgewiesen in: National Diet Library Digital Collections - 国立国会図書館デジタルコレクション Sprachen: English Contents Note: 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 ; 膀胱癌進展、浸潤におけるHGF-MET-MMP1 signalingの関与とMET阻害薬、カボザンチニブの有効性 Document Type: 博士論文 File Description: application/pdf Language: English Degree: 博士（医学） -- 徳島大学 Notes: 収集根拠 : 博士論文（自動収集） ; 資料形態 : テキストデータ ; コレクション : 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文 ; 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 < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells.CONCLUSIONS These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscleinvasive BCa.

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