Elevated Slit2 Activity Impairs VEGF-Induced Angiogenesis and Tumor Neovascularization in EphA2-Deficient Endothelium.

摘要: Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited tumors. Indeed, tumors upregulate proangiogenic molecules while simultaneously suppressing angiostatic pathways to recruit blood vessels for growth, survival, metastatic spread. Understanding how cancers exploit antiangiogenic signals a key step developing new, molecularly targeted therapies. While EphA2, receptor tyrosine kinase (RTK), required VEGF-induced angiogenesis, the mechanism through these intersect remains unclear. Slit2 expression elevated EphA2-deficient endothelium, here it reported that inhibiting Slit activity rescues angiogenesis cell culture vivo, as well VEGF-dependent tumor endothelial cells animals. Moreover, blocking or restores activation of Src Rac, both VEGF-mediated angiogenesis. These data suggest EphA2 suppression enables vitro providing plausible impaired responses VEGF absence function. Implications: Modulation factor regulates neovascularization. Mol Cancer Res; 13(3); 524–37. ©2014 AACR.