help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Theurillat, J.-P.
Right arrow Articles by Aguzzi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Theurillat, J.-P.
Right arrow Articles by Aguzzi, A.
(American Journal of Pathology. 1999;154:581-590.)
© 1999 American Society for Investigative Pathology

Regular Articles

Early Induction of Angiogenetic Signals in Gliomas of GFAP-v-src Transgenic Mice

Jean-Philippe Theurillat, Johannes Hainfellner, Alessia Maddalena, Jakob Weissenberger and Adriano Aguzzi

From the Institute of Neuropathology, Department of Pathology, Universitätsspital Zürich, Zürich, Switzerland

Angiogenesis is a prerequisite for solid tumor growth. Glioblastoma multiforme, the most common malignant brain tumor, is characterized by extensive vascular proliferation. We previously showed that transgenic mice expressing a GFAP-v-src fusion gene in astrocytes develop low-grade astrocytomas that progressively evolve into hypervascularized glioblastomas. Here, we examined whether tumor progression triggers angiogenetic signals. We found abundant transcription of vascular endothelial growth factor (VEGF) in neoplastic astrocytes at surprisingly early stages of tumorigenesis. VEGF and v-src expression patterns were not identical, suggesting that VEGF activation was not only dependent on v-src. Late-stage gliomas showed perinecrotic VEGF up-regulation similarly to human glioblastoma. Expression patterns of the endothelial angiogenic receptors flt-1, flk-1, tie-1, and tie-2 were similar to those described in human gliomas, but flt-1 was expressed also in neoplastic astrocytes, suggesting an autocrine role in tumor growth. In crossbreeding experiments, hemizygous ablation of the tumor suppressor genes Rb and p53 had no significant effect on the expression of VEGF, flt-1, flk-1, tie-1, and tie-2. Therefore, expression of angiogenic signals is an early event during progression of GFAP-v-src tumors and precedes hypervascularization. Given the close similarities in the progression pattern between GFAP-v-src and human gliomas, the present results suggest that these mice may provide a useful tool for antiangiogenic therapy research.




This article has been cited by other articles:


Home page
 Am. J. Neuroradiol.Home page
T. Kato, J. Shinoda, N. Nakayama, K. Miwa, A. Okumura, H. Yano, S. Yoshimura, T. Maruyama, Y. Muragaki, and T. Iwama
Metabolic Assessment of Gliomas Using 11C-Methionine, [18F] Fluorodeoxyglucose, and 11C-Choline Positron-Emission Tomography
AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1176 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Pal, K. Datta, and D. Mukhopadhyay
Central Role of p53 on Regulation of Vascular Permeability Factor/Vascular Endothelial Growth Factor (VPF/VEGF) Expression in Mammary Carcinoma
Cancer Res., September 1, 2001; 61(18): 6952 - 6957.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.