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Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. (Richard Palmqvist)
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. (Richard Palmqvist)
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
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2011 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 178, no 3, 1387-1394 p.Article in journal (Refereed) Published
Abstract [en]

Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.

Place, publisher, year, edition, pages
Elsevier , 2011. Vol. 178, no 3, 1387-1394 p.
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-41356DOI: 10.1016/j.ajpath.2010.12.008PubMedID: 21356388OAI: oai:DiVA.org:umu-41356DiVA: diva2:405684
Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2017-12-11Bibliographically approved

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Henriksson, Maria LEdin, SofiaDahlin, Anna MOldenborg, Per-ArneVan Guelpen, BethanyRutegård, JörgenStenling, RogerPalmqvist, Richard

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Henriksson, Maria LEdin, SofiaDahlin, Anna MOldenborg, Per-ArneÖberg, ÅkeVan Guelpen, BethanyRutegård, JörgenStenling, RogerPalmqvist, Richard
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