Vascular survival is an integral step in vascular development and essential for maintaining proper vascular functions. One of the molecular mechanisms identified to date, activation of endothelial receptor tyrosine kinases (RTKs) by polypeptide growth factors, appears to play an important role in endothelial cell survival, migration and vessel sprouting. Studies from our lab and others confirm a critical role of angiopoietins/Tie2 signaling in endothelial survival and vascular stability. Within the tumor-host cell interaction there is an imbalance between survival signals including angiopoietins and vascular endothelial growth factor (VEGF) that favor vascular survival and drug resistance and, death signals induced by radiation which lead to endothelial cell death and tumor regression. Therefore, this proposal will examine endothelial cell survival and radio resistance. The hypothesis is that a paracrine regulation between glioma cells and endothelial cells via the AngATie2 signaling pathway mediates endothelial cell survival and counteracts radiation-induced cell death, contributing to radio resistance of tumor vasculature. ? ? ?
| Shaifer, Candice A; Huang, Jianhua; Lin, Pengnain Charles (2010) Glioblastoma cells incorporate into tumor vasculature and contribute to vascular radioresistance. Int J Cancer 127:2063-75 |
