Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Exp Mol Pathol. 2011 Oct;91(2):596-602. doi: 10.1016/j.yexmp.2011.06.005. Epub 2011 Jul 20.
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 10(3) 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.
癌症干细胞（CSCs）在癌症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和耐药的治疗提供新的诊断和治疗靶点。在这里，我们建立了一个异种移植模型，其中将来自 14 个人类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。我们从三个不同的异种移植中鉴定并分离出 CD117(+)Lineage(-)的致瘤细胞。数量少至 10(3)个具有 CD117(+)Lineage(-)表型的细胞，占异种移植肿瘤细胞的<2%，就能够在小鼠模型中再生肿瘤，其致瘤潜力比 CD117(-)Lineage(-)细胞高 100 倍。从纯化的 CD117(+)Lineage(-)细胞中产生的肿瘤重现了原始肿瘤的异质性，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特征。此外，对 25 名晚期卵巢浆液性腺癌患者的免疫组化分析显示，40%（25 名患者中的 10 名）患者的 CD117 阳性免疫染色。CD117 表达与常规化疗耐药呈统计学相关（P=0.027）。总之，我们的研究表明，具有 CD117(+)表型的人类卵巢癌细胞具有 CSCs 的独特特性，包括自我更新、分化、高致瘤性和化疗耐药性。旨在靶向 CD117(+)癌细胞的未来研究可能会为卵巢癌的治疗确定更有吸引力和有效的治疗方法。
