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Targeting the Tie2/Tek receptor in astrocytomas.

Publication ,  Journal Article
Zadeh, G; Qian, B; Okhowat, A; Sabha, N; Kontos, CD; Guha, A
Published in: Am J Pathol
February 2004

Tie2 is an endothelial cell-specific receptor tyrosine kinase, whose activation is positively and negatively modulated by angiopoietin-1 and angiopoietin-2, respectively. Angiopoietin-mediated modulation of Tie2 activation contributes to normal vessel development and stability, however, its role in tumor angiogenesis is not well known. We investigated the role of Tie2 activation in malignant astrocytomas, a common and highly vascularized primary human brain tumor. We found that Tie2 expression and activation increases with increasing malignancy grade of astrocytomas. Inhibition of Tie2, using a kinase-deficient Tie2 construct, decreases growth of malignant human astrocytoma subcutaneous and intracranial xenografts. Tie2 inactivation disrupted the tumor vascularity, with a decrease in microvascular density, increased presence of abnormally dilated vessels, and loss of interaction between endothelial cells and surrounding smooth muscle cells, all collectively resulting in increased tumor cell apoptosis. Overall, these findings strongly suggest that Tie2 activation contributes significantly to astrocytoma tumor angiogenesis and growth. We postulate that targeting Tie2 activation, either independently or in conjunction with other anti-angiogenic therapies, such as against vascular endothelial growth factor, is of potential clinical interest.

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Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

February 2004

Volume

164

Issue

2

Start / End Page

467 / 476

Location

United States

Related Subject Headings

  • Receptor, TIE-2
  • Pathology
  • Neovascularization, Pathologic
  • Neoplasm Invasiveness
  • Mice
  • In Situ Nick-End Labeling
  • Immunohistochemistry
  • Humans
  • Enzyme Activation
  • Endothelial Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Zadeh, G., Qian, B., Okhowat, A., Sabha, N., Kontos, C. D., & Guha, A. (2004). Targeting the Tie2/Tek receptor in astrocytomas. Am J Pathol, 164(2), 467–476. https://doi.org/10.1016/S0002-9440(10)63137-9
Zadeh, Gelareh, Baoping Qian, Ali Okhowat, Nesrin Sabha, Christopher D. Kontos, and Abhijit Guha. “Targeting the Tie2/Tek receptor in astrocytomas.Am J Pathol 164, no. 2 (February 2004): 467–76. https://doi.org/10.1016/S0002-9440(10)63137-9.
Zadeh G, Qian B, Okhowat A, Sabha N, Kontos CD, Guha A. Targeting the Tie2/Tek receptor in astrocytomas. Am J Pathol. 2004 Feb;164(2):467–76.
Zadeh, Gelareh, et al. “Targeting the Tie2/Tek receptor in astrocytomas.Am J Pathol, vol. 164, no. 2, Feb. 2004, pp. 467–76. Pubmed, doi:10.1016/S0002-9440(10)63137-9.
Zadeh G, Qian B, Okhowat A, Sabha N, Kontos CD, Guha A. Targeting the Tie2/Tek receptor in astrocytomas. Am J Pathol. 2004 Feb;164(2):467–476.
Journal cover image

Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

February 2004

Volume

164

Issue

2

Start / End Page

467 / 476

Location

United States

Related Subject Headings

  • Receptor, TIE-2
  • Pathology
  • Neovascularization, Pathologic
  • Neoplasm Invasiveness
  • Mice
  • In Situ Nick-End Labeling
  • Immunohistochemistry
  • Humans
  • Enzyme Activation
  • Endothelial Cells