Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth

Abstract

Summary: The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation in the prostatic epithelium (β1pc−/−), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express β1 and sEV markers; in contrast, sEVs from β1pc−/−/TRAMP or wild-type mice lack β1 and sEV markers. Our results demonstrate that β1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth. : Biological Sciences; Molecular Biology; Cell Biology; Cancer Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Cancer