Mechanisms of VEGF Availability in Prostate Cancer

Abstract

VEGF signaling is critical to neovascularization of tumors and metastatic progression. In fact, alterations in VEGF levels or in receptor phosphorylation results in suppression of vascular expansion and concomitant reduction of tumor growth and metastasis. In this proposal we explore the ability of matrix metalloproteases to modulate VEGF signaling in tumors. We found that excess of MMPs results in the release of VEGF from matrix binding sites, with increased permeability and aberrant neovascular growth. Genetic inactivation of MMP9 in the context of tumors did not affect VEGF processing, as other MMPs compensated functionally for the lack of the protease. We thus, generated a mutant VEGF protein unable to be cleaved. In this case, permeability was suppressed, but growth of vessels continued from matrix-bound VEGF.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2005
Accession Number
ADA507142

Entities

People

  • Arnaud Movoisin
  • Luisa Iruela-arispe

Organizations

  • University of California, Los Angeles

Tags

DTIC Thesaurus Topics

  • Availability
  • Biomedical Research
  • Cancer
  • Cell Line
  • Cells
  • Contractors
  • Contracts
  • Demographic Cohorts
  • Department Of Defense
  • Endothelial Cells
  • Neoplasms
  • Patent Applications
  • Patents
  • Permeability
  • Phosphorylation
  • Prostate
  • Prostate Cancer

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology