Alcohol promotes mammary tumor growth through activation of VEGF-dependent tumor angiogenesis.

Alcohol promotes mammary tumor growth through activation of VEGF-dependent tumor angiogenesis.
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酒精通过激活VEGF依赖性肿瘤血管生成来促进乳腺肿瘤的生长。

DOI:
10.3892/ol.2014.2146
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发表时间:
2014-08
期刊:
影响因子:
2.9
通讯作者:
Wang S
Wang S
中科院分区:
医学4区
文献类型:
--
作者:
Lu Y;Ni F;Xu M;Yang J;Chen J;Chen Z;Wang X;Luo J;Wang S

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饮酒已被认为是乳腺癌的一个危险因素。实验研究表明,酒精暴露促进现有乳腺肿瘤的进展。然而,这种影响的机制仍不清楚。在本研究中,血管内皮生长因子(VEGF)在酒精促进乳腺癌发展的作用进行了研究,使用小鼠异种移植模型的乳腺肿瘤和三维(3D)肿瘤/内皮细胞共培养系统。对于小鼠异种移植模型,将小鼠E0771乳腺癌细胞植入C57 BL 6小鼠的乳房脂肪垫中。这些小鼠在饮用水中暴露于酒精。对于3D共培养系统,E0771细胞和MDA-MB 231乳腺癌细胞分别与SVEC 4 - 10 EE 2和人脐静脉内皮细胞共培养。结果表明,酒精增加肿瘤血管生成,加速肿瘤生长。此外,酒精在体外和体内诱导乳腺癌细胞VEGF表达。通过SU 5416阻断VEGF信号传导抑制了3D肿瘤/内皮细胞共培养系统中的肿瘤血管生成。此外,注射SU 5416到小鼠体内抑制酒精促进的乳腺肿瘤生长。这些结果表明,酒精可能通过刺激VEGF依赖的血管生成促进乳腺肿瘤生长。
Alcohol consumption has been recognized as a risk factor for breast cancer. Experimental studies demonstrate that alcohol exposure promotes the progression of existing mammary tumors. However, the mechanisms underlying this effect remain unclear. In the present study, the role of vascular endothelial growth factor (VEGF) in alcohol promotion of breast cancer development was investigated using a mouse xenograft model of mammary tumors and a three-dimensional (3D) tumor/endothelial cell co-culture system. For the mouse xenograft model, mouse E0771 breast cancer cells were implanted into the mammary fat pad of C57BL6 mice. These mice were exposed to alcohol in their drinking water. For the 3D co-culture system, E0771 cells and MDA-MB231 breast cancer cells were co-cultured with SVEC4-10EE2 and human umbilical vein endothelial cells, respectively. The results demonstrated that alcohol increased tumor angiogenesis and accelerated tumor growth. Furthermore, it appeared that alcohol induced VEGF expression in breast cancer cells in vitro and in vivo. Blocking VEGF signaling by SU5416 inhibited tumor angiogenesis in the 3D tumor/endothelial cell co-culture system. Furthermore, injection of SU5416 into mice inhibited alcohol-promoted mammary tumor growth in vivo. These results indicate that alcohol may promote mammary tumor growth by stimulating VEGF-dependent angiogenesis.
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