Enrichment of osteosarcoma stem cells by chemotherapy.
Enrichment of osteosarcoma stem cells by chemotherapy.
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通过化疗富集骨肉瘤干细胞
DOI：
10.5732/cjc.011.10127
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发表时间：
2011-06
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
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作者：
Tang QL;Liang Y;Xie XB;Yin JQ;Zou CY;Zhao ZQ;Shen JN;Wang J
骨肉瘤是儿童和青少年最常见的原发性恶性骨癌。新出现的证据表明，肿瘤的生长能力是由肿瘤内的一小部分细胞（称为癌症干细胞（CSC））驱动的。虽然已经探索了几种方法来鉴定或富集骨肉瘤中的CSC，但这些方法有时似乎不切实际，并且很少研究骨肉瘤中CSC的化疗富集。在本研究中，我们发现短时间暴露于化疗可以改变骨肉瘤细胞的形态，增加体外肌球形成，以及增加体内肿瘤形成。此外，甲氨蝶呤（MTX）耐药的U2 OS/MTX 300骨肉瘤细胞的大小和生长更紧密比亲本U2 OS细胞。更重要的是，与亲本U2 OS细胞相比，U2 OS/MTX 300细胞在无血清条件下具有更高的产生肌球的潜力。此外，U2 OS/MTX 300细胞表现出侧群（SP）表型，并表达CSC表面标志物CD 117和Stro-1。值得注意的是，相对于U2 OS细胞，U2 OS/MTX 300细胞在裸鼠中显示出显著更高的致瘤性。因此，我们认为化疗富集是一种可行的、实用的骨肉瘤干细胞富集方法。
Osteosarcoma is the most common primary malignant bone cancer in children and adolescents. Emerging evidence has suggested that the capability of a tumor to grow is driven by a small subset of cells within a tumor, termed cancer stem cells (CSCs). Although several methods have been explored to identify or enrich CSCs in osteosarcoma, these methods sometimes seem impractical, and chemotherapy enrichment for CSCs in osteosarcoma is rarely investigated. In the present study, we found that short exposure to chemotherapy could change the morphology of osteosarcoma cells and increase sarcosphere formation in vitro, as well as increase tumor formation in vivo. Furthermore, methotrexate (MTX)-resistant U2OS/MTX300 osteosarcoma cells were larger in size and grew much more tightly than parental U2OS cells. More importantly, U2OS/MTX300 cells possessed a higher potential to generate sarcospheres in serum-free conditions compared to parental U2OS cells. Also, U2OS/MTX300 cells exhibited the side population (SP) phenotype and expressed CSC surface markers CD117 and Stro-1. Notably, U2OS/MTX300 cells showed a substantially higher tumorigenicity in nude mice relative to U2OS cells. Therefore, we conclude that chemotherapy enrichment is a feasible and practical way to enrich osteosarcoma stem cells.