Targeting the Tie2/Tek receptor in astrocytomas.

摘要: Tie2 is an endothelial cell-specific receptor tyrosine kinase, whose activation positively and negatively modulated by angiopoietin-1 angiopoietin-2, respectively. Angiopoietin-mediated modulation of contributes to normal vessel development stability, however, its role in tumor angiogenesis not well known. We investigated the malignant astrocytomas, a common highly vascularized primary human brain tumor. found that expression increases with increasing malignancy grade astrocytomas. Inhibition Tie2, using kinase-deficient construct, decreases growth astrocytoma subcutaneous intracranial xenografts. inactivation disrupted vascularity, decrease microvascular density, increased presence abnormally dilated vessels, loss interaction between cells surrounding smooth muscle cells, all collectively resulting cell apoptosis. Overall, these findings strongly suggest significantly growth. postulate targeting activation, either independently or conjunction other anti-angiogenic therapies, such as against vascular factor, potential clinical interest.