Langenfeld Elaine M, Langenfeld John
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA.
Mol Cancer Res. 2004 Mar;2(3):141-9.
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.
骨形态发生蛋白-2（BMP-2）在大多数源自患者的肺癌中高度过表达。然而，尚未确立揭示其在癌症中作用的机制。在此我们报告，BMP-2增强了正在形成的肿瘤的新血管形成。重组BMP-2刺激了将A549细胞皮下注射到胸腺裸鼠体内所形成肿瘤中的血管生成。重组BMP-2还增强了裸鼠体内含有A549细胞的基质胶塞中的血管生成。BMP-2拮抗剂头蛋白消除了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试验中血管生成减少。BMP-2诱导人主动脉内皮细胞（HAEC）和脐静脉内皮细胞形成管腔。BMP-2还刺激了HAEC的增殖。BMP-2磷酸化Smad 1/5/8和ERK-1/2以及增加Id1表达的能力进一步证明了其激活内皮细胞的能力。这项研究揭示了BMP-2增强了正在形成的肿瘤中的血管生成反应。此外，这些数据表明BMP-2对血管生成的刺激可能涉及内皮细胞的激活。
