VAR2HP recognizing heparin‐like epitopes in targeted therapy and diagnosis of tumors

The synthesis of glycosaminoglycans (GAGs) in vivo occurs with high spatiotemporal specificity, and any aberrant expression of GAGs is closely related to the occurrence of diseases. In terms of tumorigenesis, the abnormally expressed GAGs have become a potential target for the diagnosis and therapy of tumors. As previously reported, VAR2HP, a protein probe that recognizes the unique heparin (Hep)‐like epitopes, interacts with a decasaccharide structure containing at least three HexA2S(1‐4)GlcNS6S disaccharides. Its recognition epitopes are overexpressed in various tumor cells and appear promising as target molecules of multiple tumors. Herein, we found that VAR2HP used as an antineoplastic carrier could promote drug enrichment in tumor sites by targeting the specific Hep‐like epitopes on tumor cells, thereby reducing the damage to normal cells in vitro and in vivo. Moreover, VAR2HP acting on cells alone could inhibit cell proliferation, indicating that VAR2HP as a drug carrier has a dual effect of antitumor activity. Additionally, we observed that VAR2HP significantly stained cancer tissues more strongly than neighboring nonmalignant tissues. The staining was competitively inhibited by added exogenous Hep, indicating that the Hep‐like epitopes recognized by VAR2HP were a potential target molecule in tumor diagnosis. Moreover, the VAR2HP‐bound Hep‐like epitopes were found to be overexpressed in the sera of patients with hepatocellular carcinoma (HCC) but not in normal persons and patients with cirrhosis. Taken together, this study shows that VAR2HP and its heparin‐like epitopes have great potential in targeted therapy of tumors and HCC diagnosis.