Plasma fibronectin–integrin complex (pFN-integrin complex)

Plasma fibronectin–integrin complexes are specialized molecular assemblies formed by the interaction of soluble plasma fibronectin (pFN) with specific integrin receptors, primarily alpha-v beta-3 and alpha-5 beta-1, which are selectively upregulated on the surface of angiogenic endothelial cells (PMC2881795). These complexes serve as a critical homing mechanism for several anti-angiogenic peptides, such as anginex, anastellin, and CLT1, which recruit pFN from the circulation to target the tumor vasculature (PMC3314915). In the context of cancer, these complexes facilitate tumor cell survival, invasion, and metastasis, particularly within clotted plasma environments where pFN cross-links with fibrin (PubMed 20406985). Therapeutically, targeting these complexes or utilizing them as a delivery vehicle allows for the selective destruction of angiogenic vessels while sparing quiescent vasculature. The interaction triggers downstream signaling pathways, including the activation of Tie2 and the induction of a cytotoxic unfolded protein response in endothelial cells (PMC3314915). Consequently, these complexes represent a unique target for both anti-angiogenic therapy and molecular imaging of the tumor microenvironment (PMC6143111).

Other names

Plasma fibronectin–integrin complexes on angiogenic endotheliumFibrin-fibronectin-integrin complexFibronectin-integrin complexpFN-integrin complex

Anti-angiogenic peptides recruit soluble plasma fibronectin to form complexes that selectively bind to integrins, such as alpha-v beta-3 and alpha-5 beta-1, which are overexpressed on angiogenic endothelial cells. This binding triggers internalization of the complex and induces anti-angiogenic effects, including the inhibition of endothelial cell migration, induction of the unfolded protein response, and apoptosis.