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

Marianna B. Ruzinova, Rebecca A. Schoer, William Gerald, James E. Egan, Pier Paolo Pandolfi, Shahin Rafii, Katia Manova, Vivek Mittal, Robert Benezra

Research output: Contribution to journalArticle

215 Scopus citations

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 α6 and β4 integrins, matrix metalloprotease-2, and fibroblast growth factor receptor-1. Inhibition of these factors phenocopies loss of Id in in vivo angiogenesis assays.

Original languageEnglish
Pages (from-to)277-289
Number of pages13
JournalCancer Cell
Volume4
Issue number4
DOIs
StatePublished - Oct 2003
Externally publishedYes

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