Panoply™ Human ANGPT2 Over-expressing Stable Cell Line

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) is considered a highly promising target for anti-angiogenic therapy. Exosomes are small extracellular vesicles secreted by various cell types that play a crucial role in intercellular communication by delivering functional molecules to recipient cells. Currently, the expression status of ANGPT2 in tumor-derived exosomes remains unclear. Here, researchers found that HCC-derived exosomes carry ANGPT2 and deliver it to human umbilical vein endothelial cells (HUVECs) via endocytosis; this delivery process significantly promotes angiogenesis through a Tie2-independent pathway. Additionally, the researchers observed that exosomal ANGPT2 secreted by HCC cells can be internalized by recipient HUVECs and potentially recycled. Furthermore, knocking down ANGPT2 using the CRISPR-Cas system significantly inhibited angiogenesis induced by HCC-derived exosomal ANGPT2 and markedly suppressed the activation of epithelial-mesenchymal transition (EMT) in HCC cells. These results reveal a novel pathway by which HCC-derived exosomal ANGPT2 induces tumor angiogenesis-a pathway distinct from the classical ANGPT2/Tie2 signaling axis. This pathway may serve as a potential target for anti-angiogenic therapy.

In this study, researchers utilized two hepatocellular carcinoma (HCC) cell lines (Hep3B and MHCC97H) to either overexpress ANGPT2 via lentiviral infection or knock down ANGPT2 using the CRISPR/Cas system. Transwell migration assays, wound healing assays and CCK-8 assays showed that ANGPT2-overexpressing HCC cells had dramatic increases in migration and proliferation compared with those in the control, and these capabilities of ANGPT2-deficient HCC cells were notably reduced (Figure 1).

Figure 1. ANGPT2 promotes migration and proliferation of HCC in vitro. (Xie J, et al., 2020)