Placental growth factor (PlGF) and Neuropilin-1 (NRP1) interaction (PlGF-NRP1)

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that plays a critical role in pathological angiogenesis and inflammation (UniProt P49763). While PlGF primarily signals through the VEGF receptor-1 (VEGFR-1), its interaction with the co-receptor Neuropilin-1 (NRP1) significantly enhances its angiogenic activity, particularly for the PlGF-2 isoform (Migdal et al., J Biol Chem, 1998). This interaction is a key driver in the progression of various solid tumors, where it promotes tumor vascularization, recruitment of pro-angiogenic macrophages, and tumor cell survival (PubMed: 22532581). In addition to oncology, the PlGF-NRP1 axis is implicated in ocular diseases such as age-related macular degeneration and complications of pregnancy like preeclampsia (PubMed: 24603321). Therapeutic strategies targeting this interaction include decoy receptors like aflibercept, which sequesters PlGF, and monoclonal antibodies designed to block the binding interface between PlGF and NRP1 (Holash et al., PNAS, 2002). By inhibiting this pathway, researchers aim to suppress abnormal vessel growth and reduce tumor-associated inflammation with potentially fewer side effects than broad VEGF inhibition (PubMed: 17652144).

Other names

PGF-NRP1 axisPlGF-2/NRP1 complexPlacental growth factor-2 and Neuropilin-1 interactionPGFPLGFNRP1CD304BDCA4

The primary mechanism involves the sequestration of the Placental growth factor (PlGF) ligand or the blockade of its binding site on the Neuropilin-1 (NRP1) co-receptor, thereby preventing the formation of the PlGF/VEGFR-1/NRP1 signaling complex and inhibiting downstream pro-angiogenic and pro-inflammatory pathways (PubMed: 17652144, 22532581).