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STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
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2013 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 4, 1287-1297 p.Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.

Place, publisher, year, edition, pages
2013. Vol. 74, no 4, 1287-1297 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-197063DOI: 10.1158/0008-5472.CAN-12-1875ISI: 000315029800004OAI: oai:DiVA.org:uu-197063DiVA: diva2:611647
Available from: 2013-03-18 Created: 2013-03-18 Last updated: 2013-03-18Bibliographically approved

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Kiflemariam, SaraEdqvist, Per-HenrikBirgisson, HelgiSjöblom, Tobias
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