Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma

Figure 1 A schematic drawing of the structure of the glypican-3 molecule. The core protein consists of 580 amino acids, and two heparan sulfate (HS) side chains are attached close to the C-terminal portion. Cleavage by furin between Arg³⁵⁸ and Cys³⁵⁹ results in a 40-kDa N-terminal subunit and a 30-kDa C-terminal subunit linked by a disulfide bond. Monoclonal antibody GC33 recognizes an epitope at the C-terminal portion.

Figure 2 Possible roles of glypican-3 in progression of hepatocellular carcinoma. Cell surface glypican-3 (GPC3) forms a complex with Wnt and heparin-binding growth factors such as fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) via its heparan sulfate (HS) side chains and stimulates receptor-mediated signaling in hepatocellular carcinoma (HCC) cells. SULF2 expressed in HCC cells cleaves the HS to release these ligands from the GPC3/ligand complex, which may also upregulate signaling in neighboring HCC cells.