Apoptotic cues from the extracellular matrix: regulators of angiogenesis

Abstract

A variety of factors cooperate to regulate neovessel formation and persistence. Proangiogenic growth factors have remained an area of intense interest due to their capacity to promote endothelial cell (EC) proliferation and to initiate the angiogenic program. These growth factors are associated with increased cell survival, yet paradoxically, angiogenic ECs are more susceptible to apoptosis than quiescent ECs. Survival is regulated by cooperation between growth factor receptors and integrins, which are in turn governed by the composition of the local extracellular matrix (ECM). Integrin-mediated signaling is altered or disrupted by the presence of soluble, rather than matrix-bound ligands, thus providing a means by which ECM remodeling can influence both integrinand growth factor-mediated events. Ultimately, the collaboration of these factors determines whether ECs survive or die, thereby regulating neovascularization.

Endothelial progenitor cells for cancer gene therapy

“…49 However, the receptor switches to proapoptotic activity when triggered by ligands not anchored to the extracellular matrix. 50 This occurs during detachment of therapeutic EPCs from their culture matrix and during homing to the tumor. 51 EPCs derived from blood express high levels of the antioxidative enzymes MnSOD, catalase and glutathione peroxidase leading to decreased oxidative stress-induced apoptosis.…”

Integrins as a distinct subtype of dependence receptors

“…In particular, proteolytic cleavage of pre-existing matrix proteins can alter the integrity (and physical rigidity) of the local microenvironment and provide soluble ECM fragments which can antagonize integrin binding to substrate ECM. 108 When one considers the capacity of integrin-mediated adhesion to modulate both apoptotic and growth factor signaling, the sequential alterations to the ECM that occur during tissue remodeling provide an elegant mechanism to attune the responses of individual cells based on the status of a particular cell's immediate microenvironment.…”

Pharmacoproteomic Analysis of a Novel Cell-permeable Peptide Inhibitor of Tumor-induced Angiogenesis

“…8 10.1074/mcp.M110.005264 -7 the retina (42). On the other hand, casepase-8, which plays a role in p53-induced apoptosis, was activated by unligated integrin ␣ v ␤ 3 followed by apoptosis (40).…”

“…It was reported that bFGF-induced ERK activation was required for vascular angiogenesis (41). Integrin ␣ v ␤ 3 antagonist inhibited the ERK signaling lead to endothelial cell apoptosis and blockade of angiogenesis (42). Antagonists of integrin ␣ v ␤ 3 disrupt bFGF-induced neovascularization via suppressing c-Raf-ERK activation (43).…”