Liang Jinghao, Zhang Jing, Chen Fan, Lian Zhengjun, Dong Yalu, Lu Ning, Jia Yong
Department of Orthopedics, General Hospital of Xinjiang Military Command of PLA Urumqi, P. R. China.
Department of Oncology, General Hospital of Xinjiang Military Command of PLA Urumqi, P. R. China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11030-11036. eCollection 2017.
Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. Although accumulating evidence has shown that BMP9 plays important roles in the regulation of various cellular processes, the function of BMP9 in clinical osteosarcoma remains to be explored. In this study, BMP9 expression was analyzed in 55 osteosarcoma patient samples and their matching, distant non-cancerous tissues. And the roles of BMP9 in osteosarcoma cell proliferation, apoptosis and cell cycle were also examined. Our results showed that different expression level of BMP9 was detected in all osteosarcoma samples while no expression in normal tissues. Surprisingly, there was a negative association between the expression level of BMP9 and osteosarcoma grade, with low level of BMP9 being found in high histological grade osteosarcoma. Knockdown of BMP9 accelerated the proliferation of MG63, SaOS-2, and U2OS cells. BMP9 overexpression, however, induced cell apoptosis in U2OS cells. Together, these results indicated that BMP9 plays a pivotal role in osteosarcoma. Future studies defining the mechanism of BMP9 effect may lead to novel therapeutic approaches for osteosarcoma.
已知转化生长因子-β(TGF-β)可促进肿瘤迁移和侵袭。骨形态发生蛋白(BMPs)是TGF-β家族的成员,在多种人类癌细胞系中表达。尽管越来越多的证据表明BMP9在各种细胞过程的调节中发挥重要作用,但BMP9在临床骨肉瘤中的功能仍有待探索。在本研究中,分析了55例骨肉瘤患者样本及其配对的远处非癌组织中BMP9的表达情况。同时还检测了BMP9在骨肉瘤细胞增殖、凋亡和细胞周期中的作用。我们的结果显示,在所有骨肉瘤样本中均检测到不同水平的BMP9表达,而在正常组织中未检测到表达。令人惊讶的是,BMP9的表达水平与骨肉瘤分级呈负相关,在高组织学分级的骨肉瘤中发现BMP9水平较低。敲低BMP9可加速MG63、SaOS-2和U2OS细胞的增殖。然而,BMP9过表达可诱导U2OS细胞凋亡。总之,这些结果表明BMP9在骨肉瘤中起关键作用。未来确定BMP9作用机制的研究可能会为骨肉瘤带来新的治疗方法。