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

Molecular Oncology - Tập 1 Số 3 - Trang 288-302 - 2007
Elaine Y. Lin1, Jiu-feng Li2, Gabriel Bricard3, Weigang Wang4, Yan Deng5, Rani S. Sellers6, Steven A. Porcelli3, Jeffrey W. Pollard2
1Department of Medicine, Oncology Division, Albert Einstein College of Medicine, Bronx, NY, USA
2Department of Developmental and Molecular Biology, Center of Reproductive Biology and Women's Health, Albert Einstein Cancer Center, Albert Einstein College of Medicine, 607 Chanin Bldg., 1300 Morris Park Avenue, Bronx, NY 10461, USA
3Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
4Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY/USA
5Analytical and Imaging Facility, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA
6Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

Tóm tắt

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.

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