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Cancers 2014, 6(4), 2313-2329; doi:10.3390/cancers6042313

Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

1
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Received: 8 August 2014 / Revised: 5 November 2014 / Accepted: 13 November 2014 / Published: 25 November 2014
(This article belongs to the Special Issue MET in Cancer)
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Abstract

There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted. View Full-Text
Keywords: bladder cancer; urothelial carcinoma; hepatocyte growth factor; Met; tumor growth; tumor cell invasion bladder cancer; urothelial carcinoma; hepatocyte growth factor; Met; tumor growth; tumor cell invasion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lee, Y.H.; Apolo, A.B.; Agarwal, P.K.; Bottaro, D.P. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder. Cancers 2014, 6, 2313-2329.

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