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

Mol Oncol. 2007 Dec;1(3):288-302. doi: 10.1016/j.molonc.2007.10.003.


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.

Keywords: PyMT; VEGF; angiogenesis; macrophages; malignancy; mammary; mouse; progression; transgenic; tumor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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


  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Green Fluorescent Proteins