Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages

Elaine Y. Lin, Jiu feng Li, Gabriel Bricard, Weigang Wang, Yan Deng, Rani Sellers, Steven A. Porcelli, Jeffrey W. Pollard

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Genetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)-induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF-A) produced by tumor-associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF-A into tumors at the benign stages. This stimulated formation of a high-density vessel network and in macrophage-depleted mice, was followed by accelerated tumor progression. The expression of VEGF-A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage-produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion.

Original languageEnglish (US)
Pages (from-to)288-302
Number of pages15
JournalMolecular Oncology
Volume1
Issue number3
DOIs
StatePublished - Dec 2007

Keywords

  • Angiogenesis
  • Macrophages
  • Malignancy
  • Mammary
  • Mouse
  • Progression
  • PyMT
  • Transgenic
  • Tumor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    Lin, E. Y., Li, J. F., Bricard, G., Wang, W., Deng, Y., Sellers, R., Porcelli, S. A., & Pollard, J. W. (2007). Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages. Molecular Oncology, 1(3), 288-302. https://doi.org/10.1016/j.molonc.2007.10.003