Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review

Figure 1 Common lymphangiogenesis-mediating receptors. Vascular endothelial growth factor receptor C (VEGF-C), fibroblast growth factors, hepatocyte growth factor (HGF), angiopoietins, adrenomedullin promote the survival, growth, and migratory ability of lymphatic endothelial cells (LECs); Neuropilin 2 forms a complex with VEGFR-3 upon binding with VEGF-C/D, enhancing lymphangiogenesis; Sphingosine-1-phosphate induces migration, sprouting, capillary-like tube formation of LECs; HGF, platelet-derived growth factor are directly involved in lymphangiogenesis. HGF indirectly promotes VEGF-C/D expression, contributing to lymphangiogenesis. LEC: Lymphatic endothelial cell; VEGF: Vascular endothelial growth factor receptor; HGF: Hepatocyte growth factor; S1P: Sphingosine-1-phosphate; AM: Adrenomedullin; FGFs: Fibroblast growth factors; PDGF: Platelet-derived growth factor.