Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome
Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome
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具有 CD117 表型的卵巢癌细胞具有高度致瘤性，并且与化疗结果相关
DOI：
10.1016/j.yexmp.2011.06.005
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Shen, Keng
中科院分区：
文献类型：
--
作者：
Luo, Lijing;Zeng, Jianfang;Shen, Keng
肿瘤干细胞（cancer stem cells，CSCs）在肿瘤的复发和耐药中起着重要作用。从卵巢癌样本中分离和鉴定CSCs可能有助于为卵巢癌复发性疾病和耐药性的管理提供新的诊断和治疗靶点。在这里，我们开发了一种异种移植模型，其中将来自14个人卵巢浆液性腺癌组织或腹水样本的细胞植入免疫缺陷小鼠中，以测试不同卵巢癌细胞群体的致瘤潜力。我们从三种不同的异种移植物中鉴定并分离了CD 117（+）谱系（-）的致瘤细胞。在小鼠模型中，仅103个具有CD 117（+）谱系（-）表型的细胞（其占异种移植肿瘤细胞的< 2%）能够再生肿瘤，与CD 117（+）谱系（-）细胞相比，致瘤潜力增加100倍。由纯化的CD 117（+）谱系（-）细胞产生的肿瘤再现了原始的肿瘤异质性，并且可以连续产生，证明了自我更新和分化的能力，这是干细胞的两个定义性质。此外，25例晚期卵巢浆液性腺癌患者的免疫组化分析显示，40%（10/25）的患者CD 117免疫染色阳性。CD 117表达与常规化疗耐药相关（P = 0.027）。总之，我们的研究表明，具有CD 117（+）表型的人卵巢癌细胞具有CSC的独特特性，包括自我更新，分化，高致瘤潜力和化疗抗性。未来针对CD 117（+）癌细胞的研究可能会发现更有吸引力和更有效的治疗卵巢癌的疗法。(C)2011 Elsevier Inc. All rights reserved.
Cancer stem cells (CSCs) play an important role in the recurrence and drug resistance of cancer. Isolation and characterization of CSCs from ovarian cancer samples may help to provide novel diagnostic and therapeutic targets in the management of recurrent disease and drug resistance in ovarian cancer. Here, we developed a xenograft model in which cells from 14 samples of human ovarian serous adenocarcinoma tissue or ascites were implanted in immunodeficient mice to test the tumorigenic potential of different populations of ovarian cancer cells. We identified and isolated the tumorigenic cells as CD117(+)Lineage(-) from three different xenografts. As few as 103 cells with the CD117(+)Lineage(-) phenotype, which comprise < 2% of the xenograft tumor cells, were able to regenerate tumors in a mouse model, a 100-fold increase in tumorigenic potential compared to CD117(+)Lineage(-) cells. The tumors that arose from purified CD117(+)Lineage(-) cells reproduced the original tumor heterogeneity and could be serially generated, demonstrating the ability to self-renew and to differentiate, two defining properties of stem cells. Furthermore, immunohistochemistry analysis of 25 patients with advanced ovarian serous adenocarcinoma revealed positive immunostaining for CD117 in 40% (10 of 25) of patients. CD117 expression was statistically correlated with resistance to conventional chemotherapy (P = 0.027). In conclusion, our study demonstrates that human ovarian cancer cells with the CD117(+) phenotype possess the unique properties of CSCs, including self-renewal, differentiation, a high tumorigenic potential, and chemoresistance. Future studies designed to target CD117(+) cancer cells may identify more attractive and effective therapies for treatment of ovarian cancer. (C) 2011 Elsevier Inc. All rights reserved.