Hypoxia-induced exosome secretion promotes survival of African-American and Caucasian prostate cancer cells

Sci Rep. 2018 Mar 1;8(1):3853. doi: 10.1038/s41598-018-22068-4.


African American men in the United States have higher mortality due to prostate cancer (PCa) compared to other races. One reason for this disparity is the lack of in-depth understanding of the PCa biology in African Americans. For example, hypoxia in prostate tumor microenvironment is associated with adverse prognosis; still, no hypoxia-related studies have been reported in African Americans. Here, we compared African-American and Caucasian PCa cells for exosome secretion under normoxic (21% O2) and hypoxic (1% O2) conditions. All cell lines showed higher exosome secretion under hypoxia but it was clearly more prominent in African-American PCa cells. Further, under hypoxia, Rab5 (a biomarker for early endosome) was clustered in perinuclear region; and CD63 (a biomarker for exosomes and multivesicular endosomes) showed greater co-localization with actin cytoskeleton especially in African American PCa cells. Importantly, exosome biogenesis inhibitors GW4869 (10-20 µM) or DMA (10-20 µg/ml) significantly decreased cell viability and clonogenicity in PCa cells. Interestingly, we also observed higher level of lactic acid loaded in exosomes secreted under hypoxia. Overall, under chronic hypoxia, PCa cells secrete more exosomes as a survival mechanism to remove metabolic waste.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aniline Compounds / pharmacology
  • Benzylidene Compounds / pharmacology
  • Black or African American / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Exosomes / metabolism*
  • Exosomes / physiology
  • Humans
  • Hypoxia / metabolism
  • Male
  • Prognosis
  • Prostate / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Signal Transduction
  • Tetraspanin 30 / metabolism
  • Tumor Microenvironment
  • United States
  • White People / genetics
  • rab5 GTP-Binding Proteins / metabolism


  • Aniline Compounds
  • Benzylidene Compounds
  • GW 4869
  • Tetraspanin 30
  • rab5 GTP-Binding Proteins