Purpose: In this study, we aim to clarify whether exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia affect angiogenesis in endothelial cells. Methods: Exosomes derived from human liver cancer cell lines were cultured under hypoxic or normoxic conditions for 24 h, isolated using ExoQuick-TC ® , and co-cultured with HUVECs to evaluate angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC. Results: Exosomes under hypoxia remarkably enhanced tube formation of HUVECs. Both cellular and exosomal miR-155 were significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia in HUVECs, and high expression of exosomal miR-155 in preoperative plasma was significantly correlated with early recurrence. Conclusion: These results suggest that exosomes derived from HCC cells under hypoxia induce tube formation of HUVECs and that exosomal miR-155 may affect angiogenic activity in HCC.
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