Furthermore, the time-course experiment displayed that the phosphorylation of Tie2 and downstream p85 subunit of phosphatidylinositol 3-kinase (PI3Kp85) had no obvious changes after coculture with ANGPT2-overexpressing exosomes derived from HCC cells for 15 min, 30 min, 1 h, 2 h, 4 h, and 6 h respectively (Additional file 9: Figure S6), suggesting that the angiogenesis induced by HCC cell-secreted exosomal ANGPT2 was independent from Tie2, which has been usually considered as the receptor of ANGPT2. Here, ANGPT2 is linked to hepatocellular carcinoma.