Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
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DOI：
10.1016/j.molonc.2007.10.003
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发表时间：
2007-12-01
影响因子：
6.6
通讯作者：
Pollard, Jeffrey W.
中科院分区：
文献类型：
--
作者：
Lin, Elaine Y.;Li, Jiu-feng;Pollard, Jeffrey W.
多瘤中T癌蛋白（Polyoma Middle T oncoprotein, PyMT）诱导的小鼠乳腺肿瘤中巨噬细胞的基因缺失延迟了血管生成开关和恶性肿瘤的进展。为了确定肿瘤相关巨噬细胞产生的血管内皮生长因子A （VEGF-A）是否调节血管生成开关的启动，采用遗传方法恢复肿瘤良性阶段VEGF-A的表达。这刺激了高密度血管网络的形成，在巨噬细胞耗尽的小鼠中，随后加速了肿瘤的进展。VEGF-A的表达导致以巨噬细胞为主的白细胞大量浸润肿瘤。本研究提示巨噬细胞产生的VEGF通过刺激肿瘤血管生成、白细胞浸润和肿瘤细胞侵袭来调节恶性进展。(C) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
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. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.