Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth
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
Affiliations
Rachel M. DeRita
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
Aejaz Sayeed
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
Vaughn Garcia
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA
Shiv Ram Krishn
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
Christopher D. Shields
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA
Srawasti Sarker
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
Andrea Friedman
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
Peter McCue
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Sudheer Kumar Molugu
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Ulrich Rodeck
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA
Adam P. Dicker
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA
Lucia R. Languino
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; Corresponding author
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
