Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines
Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines
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DOI：
10.3892/ijo_00000265
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发表时间：
2009-05-01
影响因子：
5.2
通讯作者：
Takakura, Yoshinori
中科院分区：
文献类型：
--
作者：
Fujii, Hiromasa;Honoki, Kanya;Takakura, Yoshinori
在实体和造血系统恶性肿瘤中存在的癌症干细胞，最近已被链接到其发病机制。肉瘤是罕见的，并且以间充质分化的程度为特征。本研究的目的是证明人肉瘤细胞系，骨肉瘤MG 63，尤文氏肉瘤HTB 166，纤维肉瘤HT 1080，是否具有干细胞样特性，这可能有助于耐药。所有细胞系都具有在锚定非依赖性、血清饥饿条件下形成球形克隆扩增集落（肌球）的能力。肉瘤球具有干细胞样的特性，具有自我更新的能力，并增加了干细胞相关基因Nanog、OCT 3/4 SOX 2和DNA修复酶基因MLH 1、MSH 2的表达。肿瘤微球对阿霉素和顺铂具有较强的耐药性，而DNA修复抑制剂咖啡因可增强阿霉素和顺铂的药效，提示肿瘤微球细胞的耐药性与其有效的DNA修复能力有关。这些结果表明，人肉瘤细胞系中存在耐药性较强的干细胞样细胞群，DNA修复抑制剂可增强化疗药物对肉瘤的疗效。
The presence of cancer stem cells in both solid and hematopoietic malignancies, has been recently linked to their pathogenesis. Sarcomas are rare, and diversely characterized by degrees of mesenchymal differentiation. The aim of the current study was to demonstrate whether the human sarcoma cell lines, osteosarcoma MG63, Ewing's sarcoma HTB166, fibrosarcoma HT1080, possess the stem-like properties which may contribute to the drug-resistance. All cell lines possessed an ability to form spherical, clonal expanding colonies (sarcospheres) in anchorage-independent, serum-starved conditions. Sarcospheres showed the stem-like properties with the ability of self-renewal, and increased expression of the stem cell-related genes such as Nanog, OCT3/4 SOX2 and DNA repair enzyme genes, MLH1 and MSH2. Sarcospheres showed strong resistance to doxorubicin and cisplatin, and caffeine, a DNA repair inhibitor, enhanced the efficacy of those drugs, suggesting that the drug resistance in sarcosphere cells was partly related to the efficient DNA repair ability. These results indicate that human sarcoma cell lines contain stem-like cell populations with strong drug resistance, and DNA repair inhibitor could enhance the efficacy of chemo-drugs against sarcomas.