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

  


Authors: Ruzinova, M. B.; Schoer, R. A.; Gerald, W.; Egan, J. E.; Pandolfi, P. P.; Rafii, S.; Manova, K.; Mittal, V.; Benezra, R.
Article Title: Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors
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.
Keywords: controlled study; nonhuman; lymph nodes; mouse; phenotype; animals; mice; mice, knockout; animal tissue; cell death; gene; cells, cultured; bone marrow; neoplasm proteins; animal experiment; tumor xenograft; angiogenesis; neovascularization, pathologic; animalia; transcription factors; endothelium cell; endothelial cells; cancer inhibition; endothelium, vascular; nucleotide sequence; pten phosphohydrolase; murinae; neoplasms, experimental; transplantation, heterologous; gene loss; inhibition kinetics; down regulation; cell hypoxia; inhibitor of differentiation protein 1; receptor protein-tyrosine kinases; tumor growth; thrombospondin 1; tumor vascularization; repressor proteins; uterine neoplasms; alpha6 integrin; integrin alpha6; genetic model; receptor, fibroblast growth factor, type 1; fibroblast growth factor receptor 1; gelatinase a; beta4 integrin; integrin beta4; inhibitor of differentiation proteins; protein-tyrosine-phosphatase; matrix metalloproteinase 2; receptors, fibroblast growth factor; id gene; female; priority journal; article; bone marrow derived endothelial cell; fish proteins
Journal Title: Cancer Cell
Volume: 4
Issue: 4
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2003-10-01
Start Page: 277
End Page: 289
Language: English
DOI: 10.1016/s1535-6108(03)00240-x
PUBMED: 14585355
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0142195911&partnerID=40&md5=129fdeaa35ee17d7f93a8f4148f14a40
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Pier Paolo Pandolfi Derinaldis
    353 Pandolfi Derinaldis
  2. William L Gerald
    375 Gerald
  3. Robert Benezra
    146 Benezra
  4. Katia O Manova-Todorova
    161 Manova-Todorova
  5. Marianna Ruzinova
    6 Ruzinova
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