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Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion
Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC) invasion by secreting motility factors and extracellular matrix processing enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by contact-dependent mechanisms. To address this question we cha...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546468/ https://www.ncbi.nlm.nih.gov/pubmed/25973543 |
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author | Knuchel, Sarah Anderle, Pascale Werfelli, Patricia Diamantis, Eva Rüegg, Curzio |
author_facet | Knuchel, Sarah Anderle, Pascale Werfelli, Patricia Diamantis, Eva Rüegg, Curzio |
author_sort | Knuchel, Sarah |
collection | PubMed |
description | Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC) invasion by secreting motility factors and extracellular matrix processing enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by contact-dependent mechanisms. To address this question we characterized the interaction between fibroblasts and SW620 and HT29 colorectal cancer cells in 2D and 3D co-culture models in vitro. Here we show that fibroblasts induce contact-dependent cancer cell elongation, motility and invasiveness independently of deposited matrix or secreted factors. These effects depend on fibroblast cell surface-associated fibroblast growth factor (FGF) -2. Inhibition of FGF-2 or FGF receptors (FGFRs) signaling abolishes these effects. FGFRs activate SRC in cancer cells and inhibition or silencing of SRC in cancer cells, but not in fibroblasts, prevents fibroblasts-mediated effects. Using an RGD-based integrin antagonist and function-blocking antibodies we demonstrate that cancer cell adhesion to fibroblasts requires integrin α(v)β(5). Taken together, these results demonstrate that fibroblasts induce cell-contact-dependent colorectal cancer cell migration and invasion under 2D and 3D conditions in vitro through fibroblast cell surface-associated FGF-2, FGF receptor-mediated SRC activation and α(v)β(5) integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2-FGFRs-SRC-α(v)β(5) integrin loop might be explored as candidate therapeutic target to block colorectal cancer invasion. |
format | Online Article Text |
id | pubmed-4546468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-45464682015-08-27 Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion Knuchel, Sarah Anderle, Pascale Werfelli, Patricia Diamantis, Eva Rüegg, Curzio Oncotarget Research Paper Carcinoma-associated fibroblasts were reported to promote colorectal cancer (CRC) invasion by secreting motility factors and extracellular matrix processing enzymes. Less is known whether fibroblasts may induce CRC cancer cell motility by contact-dependent mechanisms. To address this question we characterized the interaction between fibroblasts and SW620 and HT29 colorectal cancer cells in 2D and 3D co-culture models in vitro. Here we show that fibroblasts induce contact-dependent cancer cell elongation, motility and invasiveness independently of deposited matrix or secreted factors. These effects depend on fibroblast cell surface-associated fibroblast growth factor (FGF) -2. Inhibition of FGF-2 or FGF receptors (FGFRs) signaling abolishes these effects. FGFRs activate SRC in cancer cells and inhibition or silencing of SRC in cancer cells, but not in fibroblasts, prevents fibroblasts-mediated effects. Using an RGD-based integrin antagonist and function-blocking antibodies we demonstrate that cancer cell adhesion to fibroblasts requires integrin α(v)β(5). Taken together, these results demonstrate that fibroblasts induce cell-contact-dependent colorectal cancer cell migration and invasion under 2D and 3D conditions in vitro through fibroblast cell surface-associated FGF-2, FGF receptor-mediated SRC activation and α(v)β(5) integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2-FGFRs-SRC-α(v)β(5) integrin loop might be explored as candidate therapeutic target to block colorectal cancer invasion. Impact Journals LLC 2015-05-05 /pmc/articles/PMC4546468/ /pubmed/25973543 Text en Copyright: © 2015 Knuchel 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 Knuchel, Sarah Anderle, Pascale Werfelli, Patricia Diamantis, Eva Rüegg, Curzio Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title | Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title_full | Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title_fullStr | Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title_full_unstemmed | Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title_short | Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin α(v)β(5)-mediated adhesion |
title_sort | fibroblast surface-associated fgf-2 promotes contact-dependent colorectal cancer cell migration and invasion through fgfr-src signaling and integrin α(v)β(5)-mediated adhesion |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546468/ https://www.ncbi.nlm.nih.gov/pubmed/25973543 |
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