Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells

• DOI: 10.1073/pnas.1017667108
• Publication Date: 2011-03-02T03:35:37Z
• Authors: Marc A. Antonyak; Bo Li; Lindsey K. Boroughs; Jared L. Johnson; Joseph E. Druso; Kirsten L. Bryant; David A. Holowka; Richard A. Cerione
• Keywords: Tissue transglutaminase

Tumor progression involves the ability of cancer cells to communicate with each other and neighboring normal in their microenvironment. Microvesicles (MV) derived from human have received a good deal attention because participate horizontal transfer signaling proteins between contribute invasive activity. Here we show that MV may play another important role oncogenesis. In particular, demonstrate shed by two different cells, MDAMB231 breast carcinoma U87 glioma are capable conferring onto fibroblasts epithelial transformed characteristics (e.g., anchorage-independent growth enhanced survival capability) this effect requires protein cross-linking enzyme tissue transglutaminase (tTG). We further tTG is not sufficient transform but rather it must collaborate mediate transforming actions cell-derived MV. Proteomic analyses indicated both these vesicle preparations contained tTG-binding partner cross-inking substrate fibronectin (FN). Moreover, found cross-links FN ensuing MV-mediated transfers cross-linked recipient function cooperatively activate mitogenic activities induce transformation. These findings highlight for induction cellular transformation identify as essential participants process.