Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors

Ruzinova, M. B., Schoer, R. A., Gerald, W., Egan, J. E., Pandolfi, P. P., Rafii, S., Manova, K., Mittal, V., Benezra, R. (October 2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell, 4 (4). pp. 277-289. ISSN 1535-6108

Abstract

Angiogenic defects in Id mutant mice inhibit the growth of tumor xenografts, providing a genetic model for antiangiogenic stress. Our work tests the consequences of such stress on progression of more physiological Pten(+/-) tumors. While tumor growth occurs despite impaired angiogenesis, disruption of vasculature by Id loss causes tumor cells to experience hypoxia and necrosis, the extent of which is tumor dependent. We show that bone-marrow-derived endothelial precursors contribute functionally to neovasculature of some but not all Pten(+/-) tumors, partially rescuing Id mutant phenotype. We demonstrate that loss of Id1 in tumor endothelial cells results in downregulation of several proangiogenic genes, including alpha6 and beta4 integrins, matrix metalloprotease-2, and fibroblast growth factor receptor-1. Inhibition of these factors phenocopies loss of Id in in vivo angiogenesis assays.

Item Type:	Paper
Uncontrolled Keywords:	GROWTH-FACTOR EXPRESSION PATTERNS RECEPTOR MIGRATION CANCER GENE NEOVASCULARIZATION TRANSCRIPTION SUPPRESSION INTEGRINS
Subjects:	diseases & disorders > cancer diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:	Egan, James E. Mittal, Vivek Schoer, Rebecca A.
Communities:	CSHL labs > Mittal lab
Depositing User:	Matt Covey
Date:	October 2003
Date Deposited:	02 Apr 2013 15:38
Last Modified:	02 Apr 2013 15:38
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27999

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