Abstract

Tumor-derived Extracellular Vesicles Require ß1 Integrins to Promote Anchorage-Independent Growth

Rachel DeRita, Student, Thomas Jefferson University

The ß1 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 ß1 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 mice promote anchorage-independent growth of PrCa cells.  In contrast, sEVs from cultured PrCa cells harboring a shRNA to ß1, from wild-type mice or from TRAMP mice carrying a ß1 conditional ablation in the prostatic epithelium (ß1pc-/-), do not.  We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express ß1 and sEV markers; in contrast, sEVs from ß1pc-/- /TRAMP or wild-type mice lack ß1 and sEV markers.  Our results demonstrate that ß1 integrins in tumor-derived sEVs are required for stimulation of anchorage-independent growth.