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.
DeRita, Rachel M.; Sayeed, Aejaz; Garcia, Vaughn; Krishn, Shiv Ram; Shields, Christopher D.; Sarker, Srawasti; Friedman, Andrea; McCue, Peter; Molugu, Sudheer Kumar; Rodeck, Ulrich; Dicker, Adam P.; and Languino, Lucia R., "Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth." (2019). Department of Cancer Biology Faculty Papers. Paper 151.
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