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Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230
Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129976/ https://www.ncbi.nlm.nih.gov/pubmed/27223434 http://dx.doi.org/10.18632/oncotarget.9515 |
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author | Blackwell, Christina Sherk, Christian Fricko, Maggie Ganji, Gopinath Barnette, Mary Hoang, Bao Tunstead, James Skedzielewski, Tina Alsaid, Hasan Jucker, Beat M. Minthorn, Elisabeth Kumar, Rakesh DeYoung, M. Phillip |
author_facet | Blackwell, Christina Sherk, Christian Fricko, Maggie Ganji, Gopinath Barnette, Mary Hoang, Bao Tunstead, James Skedzielewski, Tina Alsaid, Hasan Jucker, Beat M. Minthorn, Elisabeth Kumar, Rakesh DeYoung, M. Phillip |
author_sort | Blackwell, Christina |
collection | PubMed |
description | Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients. |
format | Online Article Text |
id | pubmed-5129976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51299762016-12-11 Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 Blackwell, Christina Sherk, Christian Fricko, Maggie Ganji, Gopinath Barnette, Mary Hoang, Bao Tunstead, James Skedzielewski, Tina Alsaid, Hasan Jucker, Beat M. Minthorn, Elisabeth Kumar, Rakesh DeYoung, M. Phillip Oncotarget Research Paper Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients. Impact Journals LLC 2016-05-20 /pmc/articles/PMC5129976/ /pubmed/27223434 http://dx.doi.org/10.18632/oncotarget.9515 Text en Copyright: © 2016 Blackwell et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Blackwell, Christina Sherk, Christian Fricko, Maggie Ganji, Gopinath Barnette, Mary Hoang, Bao Tunstead, James Skedzielewski, Tina Alsaid, Hasan Jucker, Beat M. Minthorn, Elisabeth Kumar, Rakesh DeYoung, M. Phillip Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title | Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title_full | Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title_fullStr | Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title_full_unstemmed | Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title_short | Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230 |
title_sort | inhibition of fgf/fgfr autocrine signaling in mesothelioma with the fgf ligand trap, fp-1039/gsk3052230 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129976/ https://www.ncbi.nlm.nih.gov/pubmed/27223434 http://dx.doi.org/10.18632/oncotarget.9515 |
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