Vascular endothelial growth factor-C and Vascular endothelial growth factor-D (VEGF-C/D)

Lymph-angiogenesis-related ligands primarily refer to Vascular endothelial growth factor-C (VEGF-C) and Vascular endothelial growth factor-D (VEGF-D), which are the principal drivers of lymphatic vessel growth [UniProt P49767, O43915]. These ligands are secreted as pro-peptides that undergo proteolytic processing to bind with high affinity to Vascular endothelial growth factor receptor-3 (VEGFR-3), and in their mature forms, to Vascular endothelial growth factor receptor-2 (VEGFR-2) [Stacker et al., 2002]. Their primary biological function is to stimulate the proliferation, migration, and survival of lymphatic endothelial cells, which is crucial for embryonic development and adult tissue fluid balance [Alitalo, 2011]. In oncology, tumor cells often overexpress these ligands to promote the formation of peritumoral lymphatic vessels, thereby facilitating the spread of cancer cells to regional lymph nodes [Karaman & Alitalo, 2014]. Beyond cancer, these ligands play roles in inflammatory diseases and are being investigated as targets for treating exudative age-related macular degeneration and lymphedema [Opthea, 2024]. Therapeutic agents like OPT-302 act as traps to neutralize these ligands, while others like VGX-100 are monoclonal antibodies designed to block their interaction with receptors [ClinicalTrials.gov]. However, inhibiting these pathways carries risks such as impaired wound healing or the development of secondary lymphedema due to disrupted lymphatic maintenance [Rockson, 2017].

Other names

VEGF-CVEGF-DVascular endothelial growth factor CVascular endothelial growth factor DFms-related tyrosine kinase 4 ligandc-fos induced growth factorFIGFVRP

Inhibition of VEGF-C and VEGF-D binding to VEGFR-2 and VEGFR-3 receptors to suppress lymphangiogenesis and vascular permeability.