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PMID: 18509509 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Molecular oncology ·Vol. 1 ·No. 3 ·2007-12-00 ·Pages 288-302

Lin EY, Li JF, Bricard G, Wang W, Deng Y, Sellers R, Porcelli SA, Pollard JW

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.

Keywords
PyMT VEGF angiogenesis macrophages malignancy mammary mouse progression transgenic tumor
MeSH Terms
Animals Disease Progression Gene Expression Regulation, Neoplastic Green Fluorescent Proteins/genetics,metabolism Macrophages/metabolism,pathology Mammary Neoplasms, Experimental/genetics,metabolism,pathology Mice Mice, Transgenic Neoplasms/genetics,metabolism,pathology Transgenes Vascular Endothelial Growth Factor A/genetics,metabolism
Chemicals
Vascular Endothelial Growth Factor A vascular endothelial growth factor A, mouse Green Fluorescent Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lin Elaine Y
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
Bricard Gabriel
Wang Weigang
Deng Yan
Sellers Rani
Porcelli Steven A
Pollard Jeffrey W
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Article Info
Journal
Molecular oncology
Abbr.
Mol Oncol
ISSN
1878-0261
DOI
10.1016/j.molonc.2007.10.003
Published
2007-12-00
Pages
288-302
Language
English
Region
United States
NLM ID
101308230
PMCID
PMC2396497
Subset
IM
Grants
NCI NIH HHS · P01 CA100324-010001 · United States
NCI NIH HHS · R01 CA094173-05 · United States
NCI NIH HHS · R01 CA094173 · United States
NCI NIH HHS · P01 CA100324-019003 · United States
NCI NIH HHS · CA RO1 94173 · United States
NCI NIH HHS · CA PO1 100324 · United States
NCI NIH HHS · P30 CA013330 · United States
NCI NIH HHS · P01 CA100324 · United States
NCI NIH HHS · P30 CA 13330 · United States
External Links
PubMed source DOI: 10.1016/j.molonc.2007.10.003 PMC Full Text View journal details
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