Yeh Lee-Chuan C
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Int J Biomed Sci. 2010 Sep;6(3):176-81.
Breast, kidney, lung, and prostate cancers are among the human cancers that show high propensity to form bone metastasis. Bone morphogenetic protein (BMP) -2 and -7 are two members of the BMP superfamily which show the most potent biological activity in stimulating bone differentiation and repair. These proteins have been used in clinical treatment of orthopedic diseases and have also been studied in different types of cancer. We report here detection of mRNA coding for three type I and one type II BMP receptors in G-402 kidney tumor cells and A-549 lung tumor cells, suggesting that these cells are responsive to BMPs. We then observed that BMP-7 inhibited cell proliferation of both cell lines in a protein concentration dependent manner in vitro. Additionally, when BMP-7-treated cells were implanted into the flank region of male nude mice, smaller tumors, compared to those formed with the untreated cells, were observed. Histological analysis showed that the masses formed at the site of implantation displayed significantly less number of tumors than the control and exhibited significant ectopic bone formation. These findings raise the possibility of BMP-7 as a therapeutic agent for kidney and lung cancers.
乳腺癌、肾癌、肺癌和前列腺癌是人类中极易发生骨转移的癌症类型。骨形态发生蛋白(BMP)-2和-7是BMP超家族的两个成员,它们在刺激骨分化和修复方面表现出最强的生物活性。这些蛋白质已用于骨科疾病的临床治疗,也在不同类型的癌症中得到研究。我们在此报告,在G-402肾肿瘤细胞和A-549肺肿瘤细胞中检测到编码三种I型和一种II型BMP受体的mRNA,这表明这些细胞对BMP有反应。然后我们观察到,BMP-7在体外以蛋白质浓度依赖的方式抑制这两种细胞系的细胞增殖。此外,当将经BMP-7处理的细胞植入雄性裸鼠的胁腹区域时,可以观察到与未处理细胞形成的肿瘤相比,肿瘤较小。组织学分析表明,植入部位形成的肿块显示出的肿瘤数量明显少于对照组,并且表现出明显的异位骨形成。这些发现增加了BMP-7作为肾癌和肺癌治疗药物的可能性。