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

Autor: Rachel M. DeRita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter McCue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: iScience, Vol 14, Iss , Pp 199-209 (2019)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2019.03.022
Popis: 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
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