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

Autor: DeRita RM; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Sayeed A; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Garcia V; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Krishn SR; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Shields CD; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Sarker S; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., Friedman A; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA., McCue P; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA., Molugu SK; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rodeck U; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA., Dicker AP; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA., Languino LR; Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: lucia.languino@jefferson.edu.
Jazyk: angličtina
Zdroj: IScience [iScience] 2019 Apr 26; Vol. 14, pp. 199-209. Date of Electronic Publication: 2019 Mar 27.
DOI: 10.1016/j.isci.2019.03.022
Abstrakt: 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 (β1 pc-/- ), 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 β1 pc-/- /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.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE