Function analysis of exosome derived from hepatocellular carcinoma cells under hypoxia for tumor angiogenesis, invasion and metastasis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Wada Hiroshi 大阪大学, 医学系研究科, 助教 (00572554)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肝細胞癌 / 血管新生 / エクソソーム / マイクロRNA

Outline of Final Research Achievements

We aim to clarify function of exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia to angiogenesis. Two human HCC cell lines (PLC/PRF/5 and HuH7) and human umbilical vein endothelial cells (HUVECs) were used. Exosomes derived from HCC cells were added to HUVECs and we evaluate their angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC. Exosomes under hypoxia remarkably enhanced tube formation of HUVECs, compared with exosomes under normxia or control. Both cellular and exosomal miR-155 was significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia. High expression of exosomal miR-155 was significantly correlated with early recurrence. These results suggest that exosomes derived from HCC cells under hypoxia promotes angiogenesis, and that exosomal miR-155 may be target of molecular therapy for HCC.

Free Research Field

医歯薬学