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

  • Knuchel, Sarah Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
  • Anderle, Pascale Swiss Institute of Bioinformatics, Lausanne, Switzerland
  • Werfelli, Patricia Department of Oncology, University Medical Center (CHUV), University of Lausanne (UNIL), Switzerland - Swiss National Centre of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
  • Diamantis, Eva Division of Clinical Pathology, Institute of Pathology, University of Bern, Switzerland
  • Rüegg, Curzio Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - Swiss National Centre of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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    05.05.2015
Published in:
  • Oncotarget. - 2015, vol. 6, no. 16, p. 14300–14317
English 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.
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304897
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