Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo
Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo
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DOI：
10.1158/0008-5472.can-06-4608
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发表时间：
2007-05-15
期刊：
影响因子：
11.2
通讯作者：
Kasper, Susan
中科院分区：
文献类型：
--
作者：
Gu, Guangyu;Yuan, Jialing;Kasper, Susan
癌症可能源自与其正常对应物具有相同特征的癌症干细胞/祖细胞。我们报告了从该样本衍生的上皮细胞系（称为 HPET，即人前列腺上皮/hTERT）中重建原始人前列腺癌样本。这些肿瘤可以用格里森评分来描述，这种分类不适用于目前开发的任何模拟人类疾病的转基因小鼠模型。免疫组织化学和蛋白质印迹分析表明它们不表达雄激素受体或p63，与报道的前列腺干细胞类似。这些细胞系还在体外表达胚胎干标记物（Oct4、Nanog 和 Sox2）以及早期祖细胞标记物（CD44 和 Nestin）。克隆衍生的 HPET 细胞在体内重建原始人类肿瘤并分化为三种前列腺上皮细胞谱系，表明它们源自共同的干/祖细胞。连续移植实验重建了肿瘤，表明亲本或克隆衍生的 HPET 细胞的一部分具有自我更新潜力。因此，该模型可以增强我们对人类肿瘤发展的理解，并为研究癌症干/祖细胞的分化、肿瘤发生、临床前测试和耐药性的发展提供机制。
Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance.