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iScience. 2019 Mar 27;14:199-209. doi: 10.1016/j.isci.2019.03.022. [Epub ahead of print]

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

Author information

1
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.
2
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA.
3
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
4
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA.
6
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
7
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.

Abstract

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.

KEYWORDS:

Biological Sciences; Cancer; Cell Biology; Molecular Biology

PMID:
30981115
DOI:
10.1016/j.isci.2019.03.022
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