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From the Department of Neuropathology,*
Freiburg
University Medical School, Freiburg, Germany, and the Department of
Molecular Cell Biology,
Max-Planck-Institute
for Physiological and Clinical Research, Bad Nauheim, Germany
Glioblastomas are highly vascular tumors which overexpress the angiogenesis factor vascular endothelial growth factor (VEGF). VEGF and its receptors, VEGF-R1 and VEGF-R2, have been shown to be necessary for embryonic angiogenesis as well as for tumor 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 critical for normal vascular development. To assess the potential role of Tie2 and its ligands angiopoietin-1 and angiopoietin-2 in tumor vascularization, we analyzed their expression pattern in human gliomas. Tie-2 was up-regulated in tumor endothelium compared to normal human brain tissue. We further observed cell type-specific up-regulation of the message for both angiopoietin-1 and angiopoietin-2 in gliomas. Whereas Ang-1 mRNA was expressed in tumor cells, Ang-2 mRNA was detected in endothelial cells of a subset of glioblastoma blood vessels. Small capillaries with few periendothelial support cells showed strong expression of Angiopoietin-2, whereas larger glioblastoma vessels with many periendothelial support cells showed little or no expression. Although the function of Tie2 and its ligands in tumor angiogenesis remains a subject of speculation, our findings are in agreement with a recently proposed hypothesis that in the presence of VEGF, local production of Ang-2 might promote angiogenesis.
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M. Hangai, T. Murata, N. Miyawaki, C. Spee, J. I. Lim, S. He, D. R. Hinton, and S. J. Ryan Angiopoietin-1 Upregulation by Vascular Endothelial Growth Factor in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1617 - 1625. [Abstract] [Full Text]
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E. Audero, I. Cascone, I. Zanon, S. C. Previtali, R. Piva, D. Schiffer, and F. Bussolino Expression of Angiopoietin-1 in Human Glioblastomas Regulates Tumor-Induced Angiogenesis : In Vivo and In Vitro Studies Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 536 - 541. [Abstract] [Full Text] [PDF]
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M. J. Currie, S. P. Gunningham, C. Han, P. A. E. Scott, B. A. Robinson, A. L. Harris, and S. B. Fox Angiopoietin-1 Is Inversely Related to Thymidine Phosphorylase Expression in Human Breast Cancer, Indicating a Role in Vascular Remodeling Clin. Cancer Res., April 1, 2001; 7(4): 918 - 927. [Abstract] [Full Text]
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K. Teichert-Kuliszewska, P. C. Maisonpierre, N. Jones, A. I.M. Campbell, Z. Master, M. P. Bendeck, K. Alitalo, D. J. Dumont, G. D. Yancopoulos, and D. J. Stewart Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2 Cardiovasc Res, February 16, 2001; 49(3): 659 - 670. [Abstract] [Full Text] [PDF]
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Q. Yu and I. Stamenkovic Angiopoietin-2 Is Implicated in the Regulation of Tumor Angiogenesis Am. J. Pathol., February 1, 2001; 158(2): 563 - 570. [Abstract] [Full Text] [PDF]
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H. Beck, T. Acker, C. Wiessner, P. R. Allegrini, and K. H. Plate Expression of Angiopoietin-1, Angiopoietin-2, and Tie Receptors after Middle Cerebral Artery Occlusion in the Rat Am. J. Pathol., November 1, 2000; 157(5): 1473 - 1483. [Abstract] [Full Text] [PDF]
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A. Otani, H. Takagi, H. Oh, S. Koyama, M. Matsumura, and Y. Honda Expressions of Angiopoietins and Tie2 in Human Choroidal Neovascular Membranes Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1912 - 1920. [Abstract] [Full Text] [PDF]
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 J. Holash, P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag, G. D. Yancopoulos, and S. J. Wiegand Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF Science, June 18, 1999; 284(5422): 1994 - 1998. [Abstract] [Full Text]
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