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Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:536-541

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:536.)
© 2001 American Heart Association, Inc.

Vascular Biology

Expression of Angiopoietin-1 in Human Glioblastomas Regulates Tumor-Induced Angiogenesis

In Vivo and In Vitro Studies

Enrica Audero; Ilaria Cascone; Ilaria Zanon; Stefano C. Previtali; Roberto Piva; Davide Schiffer; Federico Bussolino

From the Division of Molecular Angiogenesis (E.A., I.C., I.Z., F.B.), Institute for Cancer Research and Treatment, Torino, Italy; the Department of Genetics, Biology, and Biochemistry (E.A., I.C., I.Z., F.B.) and the Department of Neuroscience (R.P., D.S.), University of Torino, Torino, Italy; and the Department of Neurology and Department of Biological and Technological Research (S.C.P.), San Raffaele Scientific Institute, Milano, Italy.

Correspondence to Federico Bussolino, MD, Divisione di Angiogenesi Molecolare-I.R.C.C., Universita di Torino, Sp. 142, Km 3.95, 10060 Candiolo (Torino), Italy. E-mail fbussolino{at}ircc.unito.it

Abstract—To define a role for the angiopoietin/Tie2 system in astrocytoma angiogenesis, we examined the expression of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) in these tumors by immunohistochemistry and in situ hybridization. Furthermore, we studied in vitro the effects elicited by glioblastoma cell–secreted Ang1 or by recombinant Ang1 on functions of endothelial cells (ECs). Our observations of astrocytomas show that a stage-specific induction of angiopoietins occurs and is correlated with angiogenic phases of different intensity. Ang1 expression was found in a few astrocytes scattered in the tumor at all stages of astrocytoma progression. In blood vessels, Ang1 mRNA increased progressively in high-grade glioblastomas, in which the number of vessels was higher than in low-grade tumors. Ang2 was detected in tumor cells and in ECs in high-grade astrocytomas, whereas its expression was negligible in low-grade tumors. Coculture of glioblastoma cell lines producing Ang1 with endothelium demonstrated a key role of this ligand in the control of EC network organization. We found that recombinant Ang1 in vitro induces EC spreading and reorganization of the cell monolayer into cordlike structures. These results suggest that Ang1 directly acts on ECs by modulating cell-cell and cell-matrix associations and promoting the differentiation phase of angiogenesis.


Key Words: angiopoietins • glioblastomas • angiogenesis




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