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

AfricanAmerican 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 AfricanAmericans. For example, hypoxia in prostate tumor microenvironment is associated with adverse prognosis; still, no hypoxia-related studies have been reported in AfricanAmericans. Here, we compared African-American and Caucasian PCa cells for exosomesecretion under normoxic (21% O2) and hypoxic (1% O2) conditions. All cell lines showed higher exosomesecretion 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 exosomesand multivesicular endosomes) showed greater co-localization with actin cytoskeleton especially in AfricanAmerican PCa cells. Importantly, exosomebiogenesis 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 exosomessecreted under hypoxia. Overall, under chronic hypoxia, PCa cells secrete more exosomesas a survival mechanism to remove metabolic waste.