Accelerated growth of B16 BL 6 tumor in mice through efficient uptake of their own exosomes by B16 BL 6 cells

Exosomes are extracellular vesicles released by various cell types and play roles in cell–cell communication. Several studies indicate that cancer cell‐derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell‐derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the effect of cancer‐cell derived exosomes on tumor growth by analyzing their biodistribution. Murine melanoma B16 BL 6‐derived exosomes increased the proliferation and inhibited the apoptosis of B16 BL 6 cells, which was associated with an increase and decrease in the levels of proliferation‐ and apoptosis‐related proteins, respectively. GW 4869‐induced inhibition of exosome secretion decreased the proliferation of B16 BL 6 cells, and treatment of GW 4869‐treated cells with B16 BL 6‐derived exosomes restored their proliferation. Next, we treated B16 BL 6 tumors in mice with B16 BL 6‐derived exosomes and examined the biodistribution and cellular uptake of these exosomes. After the intratumoral injection of radiolabeled B16 BL 6‐derived exosomes, most radioactivity was detected within the tumor tissues of mice. Fractionation of cells present in the tumor tissue showed that fluorescently labeled exosomes were mainly taken up by B16 BL 6 cells. Moreover, intratumoral injection of B16 BL 6‐derived exosomes promoted tumor growth, whereas intratumoral injection of GW 4869 suppressed tumor growth. These results indicate that B16 BL 6 cells secrete and take up their own exosomes to induce their proliferation and inhibit their apoptosis, which promotes tumor progression.