Integrins in vascular development

Abstract

Many growth factors and their protein kinase receptors play a role in regulating vascular development. In addition, cell adhesion molecules, such as integrins and their ligands in the extracellular matrix, play important roles in the adhesion, migration, proliferation, survival and differentiation of the cells that form the vasculature. Some integrins are known to be regulated by angiogenic growth factors and studies with inhibitors of integrin functions and using strains of mice lacking specific integrins clearly implicate some of these molecules in vasculogenesis and angiogenesis. However, the data are incomplete and sometimes discordant and it is unclear how angiogenic growth factors and integrin-mediated adhesive events cooperate in the diverse cell biological processes involved in forming the vasculature. Consideration of the results suggests working hypotheses and raises questions for future research directions.

The epigenetic reprogramming of poorly aggressive melanoma cells by a metastatic microenvironment

“…Laminin is also an integral component of vasculogenic-like networks or fluid-conducting meshwork formed by aggressive melanoma cells in vitro and in vivo, respectively [12,19,21,74]. Thus, it is tempting to speculate that the acquired ability of poorly aggressive melanoma cells to upregulate laminin 5 (and an associated α 3 -containing integrin) and the MMPs necessary to cleave it into promigratory signals in their microenvironment provides additional evidence that they have acquired a transdifferentiated phenotype that resembles a more aggressive melanoma cell, with possible implications in altered signaling capabilities as well [81]. Quite interestingly, the inductive potential of the microenvironment preconditioned by aggressive metastatic melanoma cells can be neutralized by treatment with a chemically modified tetracycline (CMT-3 or COL-3), which is a potent inhibitor of MMP activity, inhibits the cleavage of laminin 5 chain to promigratory fragments, and down-regulates MMP-2, MMP-9, MT1-MMP, VE-cadherin, VEGF-C, and TIE-1 [31].…”

Increased expression of the β4 and α5 integrin subunits in cerebral blood vessels of transgenic mice chronically producing the pro-inflammatory cytokines IL-6 or IFN-α in the central nervous system

“…The ECM and integrins are essential for blood vessel formation and function (Stromblad and Cheresh 1996;Eliceiri and Cheresh 1999;Hynes et al 1999;Hynes et al 2002). Null mutations in fibronectin (George et al 1993) or the α4 (Yang et al 1995), α5 (Yang et al 1993), αv (Bader et al 1998) or β8 (Zhu et al 2002) integrin subunits all result in defective vascular development.…”

“…Specifically, integrin expression on cerebral blood vessels is decreased during focal cerebral ischemia Wagner et al 1997;Tagaya et al 2001) and acute demyelination events (Sobel et al 1998), but is increased during chronic inflammatory events in the demyelinating animal model, experimental autoimmune encephalomyelitis (EAE) (Previtali et al 1997), and in the facial motor nucleus lesion model (Kloss et al 1999). When taken together with the role of the ECM in regulating vascular function (Eliceiri and Cheresh 1999;Hynes et al 1999;Kim et al 2000;Milner and Campbell 2002b), this suggests that dynamic alterations in integrin expression might contribute to some of the vascular changes observed during these conditions. In light of this, it is important to examine the influence of individual cytokines on vascular cell integrin expression and function in vivo, during chronic inflammation.…”

Netrin-Integrin Signaling in Epithelial Morphogenesis, Axon Guidance and Vascular Patterning

“…10 Axon guidance, epithelial morphogenesis, and vascular patterning require dynamic control of cell adhesion and cytoskeletal organization. [11][12][13] The integrins are a large family of receptors, which attach cells to the extracellular matrix, organize their cytoskeleton, and cooperate with receptor protein tyrosine kinases to regulate these processes. 14,15 We here discuss the hypothesis that netrins exert key roles in axon guidance, branching morphogenesis, and angiogenesis by binding to certain integrins and/or modulating their signaling function.…”