Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model.
Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model.
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DOI：
10.1158/0008-5472.can-08-4673
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发表时间：
2009-11-15
期刊：
影响因子：
11.2
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Mulholland DJ;Xin L;Morim A;Lawson D;Witte O;Wu H
我们之前已经证明Pten缺失会导致CK 5和p63阳性前列腺癌细胞亚群的扩大。虽然该亚群可能参与肿瘤的发生或进展，但迄今为止的研究尚未在功能上验证这一假设。使用体外球体形成和体内前列腺重建测定，我们在此显示Pten前列腺癌小鼠模型中存在肿瘤起始亚群。具体来说，我们证明了Lin-Sca-1+ CD 49 fhigh（LSC）亚群与CK 5 +;p63+细胞重叠，并且在前列腺癌发生、进展和去势后显著增加。突变球体模拟Pten无效原发性肿瘤中上皮区室的结构组织。来自Pten无效球或原发性肿瘤的分选的LSC细胞能够再生具有癌性形态的前列腺上皮结构，非常模拟原发性癌症的形态。因此，LSC亚群能够引发癌性表型，其重现Pten突变前列腺模型的原发性病变中所见的病理。
We have previously demonstrated that Pten deletion leads to the expansion of subset of prostate cancer cells positive for CK5 and p63. While this subpopulation may be involved in tumor initiation or progression, studies to date have not functionally validated this hypothesis. Using in vitro sphere forming and in vivo prostate reconstitution assays, we show here the presence of a tumor initiating subpopulation in the Pten prostate cancer mouse model. Specifically, we demonstrate that the Lin-Sca-1+CD49fhigh (LSC) subpopulation overlaps with CK5+;p63+ cells and is significantly increased during prostate cancer initiation, progression and after castration. Mutant spheres mimic the structural organization of the epithelial compartment in the Pten null primary tumor. Sorted LSC cells from either Pten null spheres or primary tumors are able to regenerate prostate epithelial structure with cancerous morphology, closely mimicking that of primary cancers. Therefore, the LSC subpopulation is capable of initiating a cancerous phenotype that recapitulates the pathology seen in the primary lesions of Pten mutant prostate model.