CELL-TYPE-SPECIFIC EXPRESSION OF ANGIOPOIETIN-1 AND ANGIOPOIETIN-2 SUGGESTS A ROLE IN GLIOBLASTOMA ANGIOGENESIS

Glioblastomas are highly vascular tumors which overexpress the angioge nesis factor vascular endothelial growth factor (VEGF), VEGF and its r eceptors, VEGF-R1 and VEGF-R2, have been shown to be necessary for emb ryonic angiogenesis as well as for turner angiogenesis. Recently, the angiopoietin/Tie2 receptor system has been shown to exert functions in the cardiovascular system that are distinct from VEGF but are also cr itical for normal vascular development. To assess the potential role o f Tie2 and its ligands angiopoietin-1 and angiopoietin-2 in tumor vasc ularization, we analyzed their expression pattern in human gliomas, Ti e-2 was up-regulated in tumor endothelium compared to normal human bra in tissue. We further observed cell type-specific up-regulation of the message for both angiopoietin-1 and angiopoietin-2 in gliomas, Wherea s Ang-1 mRNA was expressed in tumor cells, Ang-2 mRNA was detected in endothelial cells of a subset of glioblastoma blood vessels. Small cap illaries with few periendothelial support cells showed strong expressi on of Angiopoietin-2, whereas larger glioblastoma vessels with many pe riendothelial support cells showed little or no expression. Although t he function of Tie2 and its ligands in tumor angiogenesis remains a su bject of speculation, our findings are in agreement with a recently pr oposed hypothesis that in the presence of VEGF, local production of An g-2 might promote angiogenesis.