ArticlebioRxiv : the preprint server for biology2025
Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate anti-proliferative effects.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Antibodies blocking the function of vascular endothelial growth factor A (VEGFA) remain a promising therapeutic strategy, especially when combined with check-point inhibitors, but their efficacy is limited by tumor resistance. This can occur via multiple mechanisms, including upregulation of placental growth factor 2 (PlGF-2), an alternative ligand for VEGF receptor 1 (VEGFR1) and neuropilin receptor 1 (NRP1). Activity of both growth factors is mediated by interactions with multiple receptors and extra-cellular matrix components, which complicates efforts to understand their contributions to cancer progression. To complement existing antibodies, we discovered those blocking interactions between PlGF-2 or VEGFA and their shared NRP1 receptor in the presence of heparin. Limiting angiogenesis to promote vascular normalization is one mechanism of anti-VEGF protection; here, anti-VEGFA antibodies blocking interactions with VEGFR1 and NRP1 reduced HUVEC tube formation in a physiological angiogenesis model. By contrast, antibodies binding PlGF-2 or VEGFA to block NRP1 significantly reduced proliferation of Caki-I kidney carcinoma cells
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