CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer
CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer
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DOI：
10.1002/stem.236
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发表时间：
2009-12-01
期刊：
影响因子：
5.2
通讯作者：
Foster, Rosemary
中科院分区：
文献类型：
--
作者：
Curley, Michael D.;Therrien, Vanessa A.;Foster, Rosemary
越来越多的证据表明，实体瘤含有一种罕见的表型独特的细胞群，称为癌症干细胞（CSC），它们产生并维持肿瘤的大部分。这些CSC由于其内在的干细胞样特性而被认为对当前的化疗策略具有抵抗力，因此可能提供肿瘤复发生长的主要驱动力。鉴于与人类卵巢癌相关的复发性转移的高频率，我们试图确定原发性人类卵巢肿瘤是否包含具有增强的肿瘤启动能力（CSC 的一个特征）的细胞群。使用体内连续移植模型，我们证明原发性未培养的人类卵巢肿瘤可以在 NOD/SCID 小鼠中可靠地繁殖，产生维持亲代肿瘤组织学完整性的异质肿瘤。观察到的肿瘤植入频率表明，只有某些卵巢肿瘤细胞亚群具有重现肿瘤生长的能力。对人类卵巢肿瘤候选 CSC 表面标志物表达的进一步分析表明 CD133 的表达一致。为了确定 CD133 表达是否可以定义原发性人卵巢肿瘤中的肿瘤起始细胞群，采用了荧光激活细胞分选 (FACS) 方法。将分选的 CD133(+) 和 CD133(-) 细胞群注射到 NOD/SCID 小鼠中，证实肿瘤来源的 CD133(+) 细胞具有增强的致瘤能力，并且能够重现原始异质性肿瘤。我们的数据表明，CD133 表达定义了人类卵巢癌中 NOD/SCID 肿瘤起始细胞亚群，这可能是旨在消除卵巢癌的新化疗策略的重要靶点。干细胞 2009；27:2875-2883
Evidence is accumulating that solid tumors contain a rare phenotypically distinct population of cells, termed cancer stem cells (CSC), which give rise to and maintain the bulk of the tumor. These CSC are thought to be resistant to current chemotherapeutic strategies due to their intrinsic stem-like properties and thus may provide the principal driving force behind recurrent tumor growth. Given the high frequency of recurrent metastasis associated with human ovarian cancer, we sought to determine whether primary human ovarian tumors contain populations of cells with enhanced tumor-initiating capacity, a characteristic of CSC. Using an in vivo serial transplantation model, we show that primary uncultured human ovarian tumors can be reliably propagated in NOD/SCID mice, generating heterogeneous tumors that maintain the histological integrity of the parental tumor. The observed frequency of tumor engraftment suggests only certain subpopulations of ovarian tumor cells have the capacity to recapitulate tumor growth. Further profiling of human ovarian tumors for expression of candidate CSC surface markers indicated consistent expression of CD133. To determine whether CD133 expression could define a tumor-initiating cell population in primary human ovarian tumors, fluorescence-activated cell sorting (FACS) methods were employed. Injection of sorted CD133(+) and CD133(-) cell populations into NOD/SCID mice established that tumor-derived CD133(+) cells have an increased tumorigenic capacity and are capable of recapitulating the original heterogeneous tumor. Our data indicate that CD133 expression defines a NOD/SCID tumor initiating subpopulation of cells in human ovarian cancer that may be an important target for new chemotherapeutic strategies aimed at eliminating ovarian cancer. STEM CELLS 2009;27:2875-2883