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In Vitro and In Vivo Studies on the Effects of Bone Morphogenetic Protein-7 on Human Kidney and Lung Tumor Cells

机译:骨形态发生蛋白7对人肾脏和肺肿瘤细胞影响的体外和体内研究

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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.
机译:乳腺癌,肾癌,肺癌和前列腺癌是显示出高水平形成骨转移的人类癌症。骨形态发生蛋白(BMP)-2和-7是BMP超家族的两个成员,在刺激骨分化和修复中表现出最有效的生物学活性。这些蛋白质已用于骨科疾病的临床治疗,并已在不同类型的癌症中进行了研究。我们在这里报告在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II型BMP受体的mRNA的检测,表明这些细胞对BMP有反应。然后,我们观察到BMP-7在体外以蛋白浓度依赖性的方式抑制了两种细胞系的细胞增殖。另外,当将BMP-7处理的细胞植入雄性裸鼠的侧翼区域时,与未处理的细胞相比,观察到较小的肿瘤。组织学分析表明,在植入部位形成的肿块显示出比对照组明显更少的肿瘤,并且表现出明显的异位骨形成。这些发现增加了BMP-7作为肾癌和肺癌的治疗剂的可能性。

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