Prospective identification of tumorigenic prostate cancer stem cells
Prospective identification of tumorigenic prostate cancer stem cells
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DOI：
10.1158/0008-5472.can-05-2018
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Maitland, NJ
中科院分区：
文献类型：
--
作者：
Collins, AT;Berry, PA;Maitland, NJ
现有的前列腺癌疗法根除了肿瘤内的大部分细胞。然而，大多数患者继续发展雄激素非依赖性疾病，通过目前的治疗策略仍然无法治愈。现在有越来越多的证据表明，在一些恶性肿瘤中，肿瘤细胞被组织为一个层次，起源于负责维持肿瘤的罕见干细胞。我们在这里报告的识别和表征的癌症干细胞人口从人类前列腺肿瘤，具有显着的自我更新能力。这些细胞也能够再生表型混合群体的非克隆细胞，表达分化的细胞产物，如雄激素受体和前列腺酸性磷酸酶。癌症干细胞具有CD 44（+）/alpha（2）beta（hi）（1）/CD 133（+）表型，我们利用这些标记物从一系列具有不同Gleason分级和转移状态的前列腺肿瘤中分离细胞。在任何肿瘤中大约0.1%的细胞表达这种表型，并且CD 44（+）/alpha（2）beta（hi）（1）/CD 133（+）细胞数量与肿瘤分级之间没有相关性。前列腺癌干细胞的鉴定为研究肿瘤发生过程和开发靶向干细胞的疗法提供了有力的工具。
Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44(+)/alpha(2)beta(hi)(1)/CD133(+) phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44(+)/alpha(2)beta(hi)(1)/CD133(+) cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.