Liu Yunlu, Feng Xiaobo, Zhang Yukun, Jiang Hongyan, Cai Xianyi, Yan Xinxin, Huang Zengfa, Mo Fengbo, Yang Wen, Yang Cao, Yang Shuhua, Liu Xianzhe
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
J Orthop Res. 2016 Dec;34(12):2116-2125. doi: 10.1002/jor.23245. Epub 2016 Apr 6.
Osteosarcoma has a well-recognized bimodal distribution, with the first peak in adolescence and another in the elderly age-group. The elderly patients have different clinical features and a poorer prognosis as compared to adolescents. To better understand the biological features of osteosarcoma in the elderly population, we established a new human osteosarcoma cell line from a 58-year-old man with primary chondroblastic osteosarcoma. After 6 months of continuous culture in vitro for over 50 passages, an immortalized cell line CHOS was established. The cell line was well-characterized by cytogenetic, biomarker, functional, and histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a doubling time of 36 h. Cytogenetic analysis of CHOS cells revealed the loss of chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate. The cell line was highly tumorigenic and maintained the histological characteristics and invasive nature of the original tumor. Furthermore, on immunohistochemical analysis, the xenografts and metastases were found to co-express collagen II, aggrecan, vimentin and S100A4 that resembled the original tumor cells. Our results indicate, the potential of CHOS cell line to serve as a useful tool for further studies on the molecular biology of osteosarcoma, especially in the elderly patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016.
骨肉瘤具有公认的双峰分布,第一个高峰出现在青少年期,另一个高峰出现在老年人群体。与青少年患者相比,老年患者具有不同的临床特征且预后较差。为了更好地了解老年人群体中骨肉瘤的生物学特征,我们从一名58岁患有原发性软骨母细胞性骨肉瘤的男性患者身上建立了一种新的人骨肉瘤细胞系。经过6个月的体外连续培养超过50代后,建立了永生化细胞系CHOS。通过细胞遗传学、生物标志物、功能和组织学分析对该细胞系进行了充分表征。CHOS细胞呈现纺锤形形态,倍增时间为36小时。对CHOS细胞的细胞遗传学分析显示Y染色体丢失和12号染色体增加。定量实时聚合酶链反应(RT-PCR)、蛋白质印迹和/或免疫荧光显示CHOS细胞中存在软骨母细胞、间充质和肿瘤转移标志物的表达。与骨肉瘤细胞系相比,发现CHOS细胞对顺铂和阿霉素更敏感,但对甲氨蝶呤耐药。该细胞系具有高度致瘤性,并保留了原发肿瘤的组织学特征和侵袭性。此外,免疫组织化学分析发现,异种移植物和转移灶共表达与原发肿瘤细胞相似的II型胶原蛋白、聚集蛋白聚糖、波形蛋白和S100A4。我们的结果表明,CHOS细胞系有潜力作为进一步研究骨肉瘤分子生物学的有用工具,特别是在老年患者中。©2016骨科研究协会。由威利期刊公司出版。《矫形外科学研究》第34卷:2116 - 2125页,2016年。