1. Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth
- Author
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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.
- Subjects
viruses ,virus diseases ,lcsh:Q ,Cell Biology ,Biological Sciences ,respiratory system ,urologic and male genital diseases ,lcsh:Science ,Molecular Biology ,Article ,Cancer - 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., Graphical Abstract, Highlights • sEVs from prostate cancer stimulate anchorage-independent growth of recipient cells • sEVs from tumor bearing, but not healthy, mice contain β1 integrins • sEV stimulation of anchorage-independent growth is dependent on β1 integrins • β1 down-regulation in the prostate tumor epithelium impairs EV functions, Biological Sciences; Molecular Biology; Cell Biology; Cancer
- Published
- 2019