Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages.
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.
Lin
Elaine Y
EY
Department of Developmental and Molecular Biology, Center of Reproductive Biology and Women's Health, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Li
Jiu-feng
JF
Bricard
Gabriel
G
Wang
Weigang
W
Deng
Yan
Y
Sellers
Rani
R
Porcelli
Steven A
SA
Pollard
Jeffrey W
JW
D000818:Animals; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D049452:Green Fluorescent Proteins