QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Ding, H. Articles by Guha, A. Search for Related Content PubMed PubMed Citation

Expression and hypoxic regulation of angiopoietins in human astrocytomas

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G-1X5 (H.D., L.R., X.W., N.L., A.N., A.G.); and Division of Neurosurgery, Division of Neuropathology, Department of Pathology and Laboratory Medicine, The Toronto Hospital and University of Toronto, Ontario, Canada M5T-2S8 (P.S., A.G.)

² Address correspondence and reprint requests to Abhijit Guha, FRCSC, 2-415 McLaughlin Pav., Western Div., UHN, 399 Bathurst St., Toronto, Ontario, Canada M5T-2S8.

Abstract

Vascular endothelial growth factor (VEGF) is a major inducer of tumor angiogenesis and edema in human astrocytomas by its interaction with cognate endothelial-specific receptors (VEGFR1/R2). Tie1 and Tie2/Tek are more recently identified endothelial-specific receptors, with angiopoietins being ligands for the latter. These angiogenic factors and receptors are crucial for the maturation of the vascular system, but their role in tumor angiogenesis, particularly in astrocytomas, is unknown. In this study, we demonstrate that the angiopoietin family member Ang1 is expressed by some of the astrocytoma cell lines. In contrast to VEGF, Ang1 is down regulated by hypoxia. Ang2 was not overexpressed. Expression profiles of low-grade astrocytoma specimens were similar to those of normal brain, with low levels of Ang1, Ang2, and VEGF expression. Glioblastoma multiforme expressed higher levels of Ang1, but not to the same degree as pseudopalisading astrocytoma cells around necrotic and hypoxic zones expressed VEGF, as shown in previous studies. Ang2 expression in the highly proliferative tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek. The expression profile of these angiogenic factors and their endothelial cell receptors in human glioblastomas multiforme was similar to that in a transgenic mouse model of glioblastoma multiforme. These data suggest that both VEGF and angiopoietins are involved in regulating tumor angiogenesis in human astrocytomas.

This article has been cited by other articles:

				E. R. Smith, D. Zurakowski, A. Saad, R. M. Scott, and M. A. Moses Urinary Biomarkers Predict Brain Tumor Presence and Response to Therapy Clin. Cancer Res., April 15, 2008; 14(8): 2378 - 2386. [Abstract] [Full Text] [PDF]

				Q. Zhou, P. Guo, and J. M. Gallo Impact of Angiogenesis Inhibition by Sunitinib on Tumor Distribution of Temozolomide Clin. Cancer Res., March 1, 2008; 14(5): 1540 - 1549. [Abstract] [Full Text] [PDF]

				W. S.N. Shim, I. A.W. Ho, and P. E.H. Wong Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis Mol. Cancer Res., July 1, 2007; 5(7): 655 - 665. [Abstract] [Full Text] [PDF]

				G. Niu and W. B. Carter Human Epidermal Growth Factor Receptor 2 Regulates Angiopoietin-2 Expression in Breast Cancer via AKT and Mitogen-Activated Protein Kinase Pathways Cancer Res., February 15, 2007; 67(4): 1487 - 1493. [Abstract] [Full Text] [PDF]

				K. E. Fathers, C. M. Stone, K. Minhas, J. J.A. Marriott, J. D. Greenwood, D. J. Dumont, and B. L. Coomber Heterogeneity of Tie2 Expression in Tumor Microcirculation: Influence of Cancer Type, Implantation Site, and Response to Therapy Am. J. Pathol., December 1, 2005; 167(6): 1753 - 1762. [Abstract] [Full Text] [PDF]

				P. Shannon, N. Sabha, N. Lau, D. Kamnasaran, D. H. Gutmann, and A. Guha Pathological and Molecular Progression of Astrocytomas in a GFAP:12V-Ha-Ras Mouse Astrocytoma Model Am. J. Pathol., September 1, 2005; 167(3): 859 - 867. [Abstract] [Full Text] [PDF]

				P. Yang, O. Agapova, A. Parker, W. Shannon, P. Pecen, J. Duncan, M. Salvador-Silva, and M. R. Hernandez DNA microarray analysis of gene expression in human optic nerve head astrocytes in response to hydrostatic pressure Physiol Genomics, April 13, 2004; 17(2): 157 - 169. [Abstract] [Full Text] [PDF]

				G. Zadeh, B. Qian, A. Okhowat, N. Sabha, C. D. Kontos, and A. Guha Targeting the Tie2/Tek Receptor in Astrocytomas Am. J. Pathol., February 1, 2004; 164(2): 467 - 476. [Abstract] [Full Text] [PDF]

				S. Khatua, K. M. Peterson, K. M. Brown, C. Lawlor, M. R. Santi, B. LaFleur, D. Dressman, D. A. Stephan, and T. J. MacDonald Overexpression of the EGFR/FKBP12/HIF-2{alpha} Pathway Identified in Childhood Astrocytomas by Angiogenesis Gene Profiling Cancer Res., April 15, 2003; 63(8): 1865 - 1870. [Abstract] [Full Text] [PDF]

				M. van den Bent, O.-L. Chinot, and J. G. Cairncross Recent developments in the molecular characterization and treatment of oligodendroglial tumors Neuro-oncol, April 1, 2003; 5(2): 128 - 138. [Abstract] [PDF]