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

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 cul...

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Autores principales: Lee, Young H., Apolo, Andrea B., Agarwal, Piyush K., Bottaro, Donald P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276968/
https://www.ncbi.nlm.nih.gov/pubmed/25534569
http://dx.doi.org/10.3390/cancers6042313
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author Lee, Young H.
Apolo, Andrea B.
Agarwal, Piyush K.
Bottaro, Donald P.
author_facet Lee, Young H.
Apolo, Andrea B.
Agarwal, Piyush K.
Bottaro, Donald P.
author_sort Lee, Young H.
collection PubMed
description 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.
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spelling pubmed-42769682015-01-15 Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder Lee, Young H. Apolo, Andrea B. Agarwal, Piyush K. Bottaro, Donald P. Cancers (Basel) Article 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. MDPI 2014-11-25 /pmc/articles/PMC4276968/ /pubmed/25534569 http://dx.doi.org/10.3390/cancers6042313 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Young H.
Apolo, Andrea B.
Agarwal, Piyush K.
Bottaro, Donald P.
Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title_full Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title_fullStr Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title_full_unstemmed Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title_short Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder
title_sort characterization of hgf/met signaling in cell lines derived from urothelial carcinoma of the bladder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276968/
https://www.ncbi.nlm.nih.gov/pubmed/25534569
http://dx.doi.org/10.3390/cancers6042313
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