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Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis.
Cellular and Molecular Life Sciences
New blood vessel formation, a process referred to as angiogenesis, is essential for embryonic development and for many physiological and pathological processes during postnatal life, including cancer progression. Endothelial cell adhesion molecules of the integrin family have emerged as critical mediators and regulators of angiogenesis and vascular homeostasis. Integrins provide the physical interaction with the extracellular matrix necessary for cell adhesion, migration and positioning, and induction of signaling events essential for cell survival, proliferation and differentiation. Antagonists of integrin alpha V beta 3 suppress angiogenesis in many experimental models and are currently tested in clinical trials for their therapeutic efficacy against angiogenesis-dependent diseases, including cancer. Furthermore, interfering with signaling pathways downstream of integrins results in suppression of angiogenesis and may have relevant therapeutic implications. In this article we review the role of integrins in endothelial cell function and angiogenesis. In the light of recent advances in the field, we will discuss their relevance as a therapeutic target to suppress tumor angiogenesis.
Animals, Blood Vessels/cytology, Blood Vessels/growth & development, Cell Adhesion Molecules/physiology, Cell Survival, Cyclooxygenase 2, Endothelium, Vascular/cytology, Endothelium, Vascular/physiology, Homeostasis, Humans, Integrins/physiology, Isoenzymes/metabolism, Lymphatic System/cytology, Lymphatic System/growth & development, MAP Kinase Signaling System, Membrane Microdomains/metabolism, Membrane Proteins, Models, Biological, NF-kappa B/metabolism, Neovascularization, Pathologic, Neovascularization, Physiologic, Prostaglandin-Endoperoxide Synthases/metabolism, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-akt, Signal Transduction, rho GTP-Binding Proteins/metabolism
Web of science
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