Integrins team up with tyrosine kinase receptors and plexins to control angiogenesis.
OBJECTIVE
Understanding the role of integrins in the formation of vascular bed is important for designing new therapeutic approaches to ameliorate or inhibit pathological vascularization. Besides regulating cell adhesion and migration, integrins dynamically participate in a network with soluble molecules and their receptors. This study summarizes recent progress in the understanding of the reciprocal interactions between integrins, tyrosine kinase, and semaphorin receptors.


RESULTS
During angiogenic remodeling, endothelial cells that line blood vessel walls dynamically modify their integrin-mediated adhesive contacts with the surrounding extracellular matrix. During angiogenesis, opposing autocrine and paracrine loops of growth factors and semaphorins regulate endothelial integrin activation and function through tyrosine kinase receptors and the neuropilin/plexins system. Moreover, proangiogenic and antiangiogenic factors can directly bind integrins and regulate endothelial cell behavior. Studies describing these intense research areas are discussed.


CONCLUSIONS
Alteration in the balance between the angiogenic growth factors and semaphorins results in an impairment of integrin functions and could account for cardiovascular malformation and structural and functional abnormalities of the tumor vasculature.
Serini
Guido
G
Department of Oncological Sciences, Institute for Cancer Research and Treatment, University of Torino, Candiolo, Italy.
Napione
Lucia
L
Bussolino
Federico
F
D000818:Animals; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*
D016023:Integrins; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases