Prognostic impact of CD133 expression as a tumor-initiating cell marker in endometrial cancer
Prognostic impact of CD133 expression as a tumor-initiating cell marker in endometrial cancer
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DOI：
10.1016/j.humpath.2010.05.006
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发表时间：
2010-11-01
期刊：
影响因子：
3.3
通讯作者：
Inoue, Masaki
中科院分区：
文献类型：
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作者：
Nakamura, Mitsuhiro;Kyo, Satoru;Inoue, Masaki
肿瘤启动细胞被认为是肿瘤生长的主要来源，并可能成为一个有吸引力的治疗靶点。本研究分析了CD133作为肿瘤起始细胞标记物在子宫内膜癌中的作用，并探讨了该标记物表达对预后的影响。对6株子宫内膜癌细胞进行流式细胞术分析，发现CD133(+)细胞在不同细胞类型中的频率差异很大，Ishikawa和MFE280细胞中CD133(+)细胞的比例明显较高(10%~20%)，因此需要进行后续的分析。分离的CD133(+)细胞在裸鼠或NOD/SCID小鼠体内表现出比CD133(-)细胞更具侵袭性的增殖能力和更强的致瘤性，并同时产生CD133(+)和CD133(-)细胞。此外，与CD133(-)细胞相比，它们对顺铂或紫杉醇诱导的细胞毒性具有明显的抵抗力。CD133(+)细胞的S期细胞比例高于CD133(-)细胞，血清饥饿引起的G0/G1期聚集降低了CD133(+)细胞的数量。最后，我们用免疫组织化学方法分析了62例子宫内膜癌组织中CD133的表达。CD133的表达与肿瘤的临床病理特征无明显相关性。然而，Kaplan-Meier分析显示，CD133高表达的肿瘤总体生存率低于低CD133表达的肿瘤(P=0.023，log-ranch检验)；Cox回归风险模型发现CD133高表达是一个独立的预后因素(P=0.045)。因此，本研究表明CD133不仅是子宫内膜癌的启动细胞标记物，也是判断其预后的重要标记物。(C)2010 Elsevier Inc.保留所有权利。
Tumor-initiating cells are known to be the major source of tumor propagation and might be an attractive therapeutic target. The present study dissected the roles of CD133 as a tumor-initiating cell marker in endometrial cancer and investigated the prognostic impact of this marker expression. Flow cytometry using 6 endometrial cancer cell lines revealed that the frequency of CD133(+) cells varied widely among the cell types and that Ishikawa and MFE280 cells contained significantly higher ratio (10%-20%) of such cells; therefore, these were subjected to the subsequent analyses. Sorted CD133(+) cells showed more aggressive proliferative potential in vitro and more increased tumorigenicity in nude or NOD/SCID mice than CD133(-) cells and generated both CD133(+) and CD133(-) cells. Furthermore, they showed apparent resistance to cisplatin- or paclitaxel-induced cytotoxicity compared with CD133(-) cells. CD133(+) cells had a greater S-phase fraction than CD133(-) cells, and the serum starvation that induced G0/G1 accumulation decreased the population of CD133(+) cells. Finally, we immunohistochemically analyzed the CD133 expression in endometrial cancer specimens from 62 patients. CD133 expression was not significantly associated with any of the clinicopathologic characteristic of tumors. However, the Kaplan-Meier analysis revealed that tumors with high CD133 expression showed worse overall survival (P=.023, log-rank test) than those with low CD133 expression; and the Cox regression hazard model found that high CD133 expression was an independent prognostic factor (P=.045). Thus, the present study demonstrates that CD133 is not only a tumor-initiating cell marker but also a critical prognostic marker in endometrial cancer. (C) 2010 Elsevier Inc. All rights reserved.