T-cadherin suppresses angiogenesis in vivo by inhibiting migration of endothelial cells

Abstract

Our previous studies have revealed the abundant expression of T-cadherin--a glycosylphosphatidylinositol (GPI)-anchored member of cadherin superfamily--in endothelial and mural cells in the heart and vasculature. The upregulation of T-cadherin in vascular proliferative disorders such as atherosclerosis and restenosis suggests the involvement of T-cadherin in vascular growth and remodeling. However, the functional significance of this molecule in the vasculature remains unknown. The effect of T-cadherin on angiogenesis in vivo was evaluated using Matrigel implant model. We demonstrate that T-cadherin overexpression in L929 cells injected in Matrigel inhibits neovascularization of the plug. In vitro T-cadherin inhibits the directional migration of endothelial cells, capillary growth, and tube formation but has no effect on endothelial cell proliferation, adhesion, or apoptosis in vitro. These data suggest that T-cadherin expressed in the stroma could act as a negative guidance cue for the ingrowing blood vessels and thus could have an important potential therapeutic application.

T-cadherin Supports Angiogenesis and Adiponectin Association with the Vasculature in a Mouse Mammary Tumor Model

“…First, T-cadherin confers homophilic binding between cells (7), and this engagement is reported to decrease adhesion, enhance migration, and induce proliferation of endothelial cells (16,17). Moreover, ectopic T-cadherin expression in the capillary microenvironment in vivo repulses blood vessels and stops their growth (37). Thus, inactivation of T-cadherin in vivo might be expected to increase vascularization.…”

Cadherin 13 in cancer

“…Conversely, CDH13 down-regulation in cancerous cells may promote neovascularization, as suggested by an in vivo model where the presence CDH13-overexpressing cells in implanted Matrigel plugs inhibited their neovascularization (Rubina et al, 2007).…”

Malignant Transformation in Skin is Associated with the Loss of T-Cadherin Expression in Human Keratinocytes and Heterogeneity in T-Cadherin Expression in Tumor Vasculature

“…These data indicate that the contradictory results on tumor progression could be due to the complex cancer, stromal and endothelial cell intracellular interactions inside the growing tumor. The possible mechanism underlying the function of T-cadherin in angiogenesis could be the regulation of the trajectory of the growing blood vessels, thus T-cadherin acts as a navigating receptor (Rubina et al, 2007). A diversity of navigating receptors has been already identified and shown to be involved in regulation of angiogenesis during embryogenesis and regeneration.…”