Hepatocellular carcinoma cell-derived small extracellular vesicles-associated CD147 may serve as a facilitating diagnostic marker and promotes endothelial cell angiogenesis via PI3K/Akt pathway

Abstract CD147 is thought to promote tumor angiogenesis mostly through its ability to increase expression of vascular endothelial growth factor (VEGF) in tumor cells. In the present study, we found that the expression of CD147 was significantly higher in hepatocellular carcinoma (HCC) tissue samples than in normal tissues. We also found a significantly larger number of CD147-positive small extracellular vesicles (CD147+ sEVs) in the plasma of HCC patients than those from live cirrhosis (LC) patients and healthy donors (HD). Our data demonstrate a close correlation between ration of CD147+ sEVs with progression of HCC. The index of CD147+ sEVs combined with that of alpha-fetoprotein (AFP) improves the diagnostic efficiency for HCC. and When AFP is negative, the index of CD147+ sEVs still remains a good diagnostic power. Furthermore, we show that hepatocellular carcinoma cell (HepG2)-derived CD147+ sEVs promote cell proliferation, migration, invasion and angiogenesis of human umbilical vein endothelial cells. The CD147+ sEVs up-regulates vascular endothelial growth factor A (VEGFA) by activating PI3K/Akt pathway, thereby promoting angiogenesis. Taken together, our data suggest that HCC-derived sEVs is able to promote angiogenesis through CD147 and demonstrate a diagnostic value of plasma CD147+ sEVs for HCC.