1. Extracellular matrix protein βig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation
- Author
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Michael B. Datto, Xiao-Fan Wang, Anthony Wai Ming Cheng, Yu Rong, Shideng Bao, Timothy J. Yeatman, Fumin Lin, Chaoyu Ma, Barbara A. Centeno, Shibo Jiang, and Daniel R. Radiloff
- Subjects
Integrins ,Lung Neoplasms ,Stromal cell ,Molecular Sequence Data ,Mice, SCID ,Biology ,medicine.disease_cause ,Metastasis ,Mice ,Antigens, CD ,Transforming Growth Factor beta ,Cancer stem cell ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Receptors, Vitronectin ,Amino Acid Sequence ,Extracellular Matrix Proteins ,Tumor microenvironment ,Neovascularization, Pathologic ,Endothelial Cells ,Cadherins ,medicine.disease ,Extravasation ,Extracellular Matrix ,Intercellular Junctions ,Colonic Neoplasms ,Cancer cell ,Immunology ,Cancer research ,Endothelium, Vascular ,Carcinogenesis ,Oligopeptides ,Research Paper ,Developmental Biology ,TGFBI - Abstract
Metastasis, the major cause of cancer death, is a multistep process that requires interactions between cancer cells and stromal cells and between cancer cells and extracellular matrix. Molecular alterations of the extracellular matrix in the tumor microenvironment have a considerable impact on the metastatic process during tumorigenesis. Here we report that elevated expression of βig-h3/TGFBI (transforming growth factor, β-induced), an extracellular matrix protein secreted by colon cancer cells, is associated with high-grade human colon cancers. Ectopic expression of the βig-h3 protein enhanced the aggressiveness and altered the metastatic properties of colon cancer cells in vivo. Inhibition of βig-h3 expression dramatically reduced metastasis. Mechanistically, βig-h3 appears to promote extravasation, a critical step in the metastatic dissemination of cancer cells, by inducing the dissociation of VE-cadherin junctions between endothelial cells via activation of the integrin αvβ5–Src signaling pathway. Thus, cancers associated with overexpression of βig-h3 may have an increased metastatic potential, leading to poor prognosis in cancer patients.
- Published
- 2008