Tumor-Derived Extracellular Vesicles Require ?1 Integrins to Promote Anchorage-Independent Growth.

ABSTRACT: The ?1 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 ?1 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 ?1, from wild-type mice or from TRAMP mice carrying a ?1 conditional ablation in the prostatic epithelium (?1pc-/-), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express ?1 and sEV markers; in contrast, sEVs from ?1pc-/-/TRAMP or wild-type mice lack ?1 and sEV markers. Our results demonstrate that ?1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth.

SUBMITTER: DeRita RM 

PROVIDER: S-EPMC6461598 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature