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 journalArticlepeer-review

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
Pages (from-to)288-302
Number of pages15
JournalMolecular Oncology
Volume1
Issue number3
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Animals
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins
  • Macrophages
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Transgenic
  • Neoplasms
  • Transgenes
  • Vascular Endothelial Growth Factor A

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