Lactadherin promotes VEGF-dependent neovascularization (Nature Medicine, 11:499-506, May 2005)

報告日期: 2005/10/21
報告時間: 15:10/16:00
報告學生: 楊玫琳
講評老師: 吳梨華
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Lactadherin promotes VEGF-dependent neovascularization

Nature Medicine 11, 499 - 506 (2005)

Speaker: 楊玫琳

Commentator: 吳梨華 老師

Time: Oct.21, 2005, 15:10-16:00

Place: Room 602

Abstract:

Neovascularization is a complex process and is involving numerous growth factors. Among them, vascular endothelial growth factor (VEGF) represents a major factor in angiogenesis. Besides, recent studies have shown that integrins associate with growth factor receptors to regulate angiogenesis. For example, αvβ3 integrin associates with VEGF receptor and enhances VEGF-induced endothelial cell migration and proliferation. Several extracellular matrix proteins binding to integrins, such as Del-1 (developmentally regulated endothelial cell locus), are reported in related with vessel growth and promote integrin-dependent angiogenesis. Lactadherin, a glycoprotein of milk-fat globule, shares structural domain homology with Del-1 and contains an Arg-Gly-Asp (RGD) integrin-binding sequence. However, there is little evidence about the physiological function of lactadherin. In this study, the authors demonstrated that lactadherin is expressed in and around blood vessels both in mouse and human tissue. Moreover, after ischemia, the VEGF-induced angiogenesis is blocked by injecting lactadherin antibodies to mice or in lactadherin-deficient mice. Furthermore, lactadherin is necessary for VEGF-induced AKT phosphorylation in cultured endothelial cells and promotes ischemic neovascularization in vivo through interaction with αvβ3 and αvβ5 integrins. By contrast, lactadherin signaling through integrins is independent of VEGF, indicating that lactadherin promotes AKT phosphorylation through binding to αvβ3 and αvβ5 integrins and cooperates with VEGF signaling to activate the angiogenic pathway. Taken together, these data suggested that lactadherin may be a good candidate for the modulation of blood vessel growth.

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