Cross-talk mechanism between endothelial cells and hepatocellular carcinoma cells via growth factors and integrin pathway promotes tumor angiogenesis and cell migration

Tumor angiogenesis plays a central role in the development and metastasis of hepatocellular carcinoma. Cancer cells secrete angiogenic factors to recruit vascular endothelial cells and sustain tumor vascular networks, which facilitate the migration and invasion of cancer cells. Therefore, the cross-talk between vascular endothelial cells and cancer cells is vitally necessary, however, little is known about the cross-talk mechanism of these cells interaction. In the present study, the proliferation, migration, invasion and tube formation of vascular endothelial EA.hy926 cells and hepatocellular carcinoma HepG2 cells were studied by exchanging their culture medium. The time-dependent differences of integrins induced signaling pathway associated with cell migration were investigated. Our results showed that HepG2 cells markedly enhanced the proliferation and migration ability as well as the tube formation of EA.hy926 cells by releasing growth factors. Also, the EA.hy926 cells promoted the proliferation, migration and invasion ability of HepG2 cells. The further analysis demonstrated that the integrins-FAK-Rho GTPases signaling events in both of two cells was activated under conditioned medium, and the signaling molecules in two cell lines showed a different time-dependent expression within 1h. These findings reveal the cross-talk mechanism between the endothelial cells and hepatocellular carcinoma cells, which were expected to find out new ideas for the prevention and treatment of hepatocellular carcinoma.