Bone morphogenetic protein-2 stimulates angiogenesis in developing tumors.
Bone morphogenetic protein-2 stimulates angiogenesis in developing tumors.
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DOI：
10.1158/1541-7786.141.2.3
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发表时间：
2004-03
期刊：
影响因子：
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通讯作者：
Elaine M Langenfeld;J. Langenfeld
中科院分区：
文献类型：
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作者：
Elaine M Langenfeld;J. Langenfeld
骨形态发生蛋白-2（BMP-2）在大多数患者来源的肺癌中高度过表达。然而，揭示其在癌症中作用的机制尚未建立。在这里，我们报告说，BMP-2增强发展中肿瘤的新血管形成。重组BMP-2刺激由皮下注射A549细胞形成的肿瘤中的血管形成。移植到胸腺裸鼠体内。重组BMP-2还增强裸鼠中含有A549细胞的Matrigel塞中的血管生成。BMP-2拮抗剂noggin消除BMP-2诱导的血管生成反应。此外，BMP-2 cDNA的反义转染导致基质胶测定中血管形成的减少。BMP-2诱导人主动脉内皮细胞（HAEC）和脐静脉内皮细胞中的管形成。BMP-2也能促进HAEC的增殖。BMP-2激活内皮细胞的能力通过其磷酸化Smad 1/5/8和ERK-1/2以及增加Id 1表达的能力进一步证明。这项研究表明，BMP-2增强了发展中肿瘤的血管生成反应。此外，这些数据表明，BMP-2刺激血管生成可能涉及激活内皮细胞。
Bone Morphogenetic Protein-2 (BMP-2) is highly overexpressed in the majority of patient-derived lung carcinomas. However, a mechanism revealing its role in cancer has not been established. Here we report that BMP-2 enhances the neovascularization of developing tumors. Recombinant BMP-2 stimulated blood vessel formation in tumors formed from A549 cells injected s.c. into thymic nude mice. Recombinant BMP-2 also enhanced angiogenesis in Matrigel plugs containing A549 cells in nude mice. The BMP-2 antagonist noggin abrogated BMP-2-induced angiogenic response. Furthermore, antisense transfection of BMP-2 cDNA resulted in a decrease in blood vessel formation in the Matrigel assays. BMP-2 induced tube formation in both human aortic endothelial cells (HAEC) and umbilical vein endothelial cells. BMP-2 also stimulated proliferation of HAEC. The ability of BMP-2 to activate endothelial cells was further demonstrated by its ability to phosphorylate Smad 1/5/8 and ERK-1/2 and to increase expression of Id1. This study reveals that BMP-2 enhanced the angiogenic response in developing tumors. Furthermore, these data suggest that BMP-2 stimulation of angiogenesis may involve the activation of endothelial cells.