Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion.

Details

Serval ID
serval:BIB_AD236634E8C0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion.
Journal
Oncotarget
Author(s)
Knuchel S., Anderle P., Werfelli P., Diamantis E., Rüegg C.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
6
Number
16
Pages
14300-14317
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 αvβ5. 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 αvβ5 integrin-dependent cancer cell adhesion to fibroblasts. The FGF-2-FGFRs-SRC-αvβ5 integrin loop might be explored as candidate therapeutic target to block colorectal cancer invasion.
Keywords
Cell Adhesion/physiology, Cell Communication/physiology, Cell Movement/physiology, Colorectal Neoplasms/genetics, Colorectal Neoplasms/metabolism, Fibroblast Growth Factor 2/metabolism, HEK293 Cells, HT29 Cells, Human Umbilical Vein Endothelial Cells, Humans, Neoplasm Invasiveness, Receptors, Fibroblast Growth Factor/metabolism, Receptors, Vitronectin/metabolism, Signal Transduction, Transcriptome, src-Family Kinases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/08/2015 18:47
Last modification date
20/08/2019 16:17
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