STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

Department of Oncology, Hospital Universitario Puerta de Hierro, Majadahonda.
Cancer Research (Impact Factor: 9.33). 12/2012; 73(4). DOI: 10.1158/0008-5472.CAN-12-1875
Source: PubMed


PDGF receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAFs). Elevated expression of PDGF receptors on stromal CAFs are associated with metastasis and poor prognosis, but mechanism(s) that underlie this these connections are not understood. Here 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 co-cultured 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.

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    • "A considerable number of studies demonstrate that STC1 promotes tumor migration and invasion [9], [18], [20], [31], with the exception of two studies in breast and ovarian cancer [32], [33]. These inconsistent results may be due to the dynamic and complicated regulatory functions of STC1 in cell growth and apoptosis [8]. "
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