Open AccessVascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
Author(s) -
Lin Elaine Y.,
Li Jiu-feng,
Bricard Gabriel,
Wang Weigang,
Deng Yan,
Sellers Rani,
Porcelli Steven A.,
Pollard Jeffrey W.
Publication year - 2007
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2007.10.003
Subject(s) - angiogenesis , vascular endothelial growth factor , tumor progression , infiltration (hvac) , cancer research , macrophage , biology , malignancy , neovascularization , pathology , vascular endothelial growth factor a , vegf receptors , medicine , cancer , in vitro , biochemistry , genetics , physics , thermodynamics
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.