CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis.

CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis.
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CD44+ CD24( - )前列腺细胞是早期的癌症祖/干细胞,为预后不良的患者提供了模型。

DOI:
10.1038/sj.bjc.6604242
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发表时间:
2008-02-26
影响因子:
8.8
通讯作者:
Farrar, W. L.
Farrar, W. L.
中科院分区:
医学1区
文献类型:
--
作者:
Hurt, E. M.;Kawasaki, B. T.;Klarmann, G. J.;Thomas, S. B.;Farrar, W. L.

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最近的证据支持这一假设,即癌症干细胞负责肿瘤的起始和形成。使用流式细胞术,我们分离了一群CD 44 + CD 24 −前列腺细胞,这些细胞显示干细胞特征以及预测前列腺癌患者总生存率的基因表达模式。CD 44 + CD 24 −细胞在软琼脂中形成集落,当注射100个细胞时,在NOD/SCID小鼠中形成肿瘤。此外,CD 44 + CD 24 −细胞表达已知在干细胞维持中重要的基因,如BMI-1和Oct-3/4。此外,我们可以在血清替代培养基中维持CD 44 + CD 24 −前列腺干细胞样细胞作为非粘附球体,而不会显著改变基因表达。添加血清导致粘附到塑料上,并改变基因表达模式以类似于分化的亲本细胞。因此,我们提出CD 44 + CD 24 −前列腺细胞是负责肿瘤起始的干细胞样细胞,我们提供了这些细胞及其产生的分化细胞的基因组定义。此外,CD 44 + CD 24 −细胞的基因表达模式具有预测患者预后不良的基因组特征。因此,CD 44 + CD 24 − LNCaP前列腺细胞提供了一个有吸引力的模型系统,既可以探索对前列腺癌干细胞的维持和分化重要的生物学,也可以开发治疗方法,因为这些细胞中的基因表达模式与前列腺癌患者的生存率低一致。
Recent evidence supports the hypothesis that cancer stem cells are responsible for tumour initiation and formation. Using flow cytometry, we isolated a population of CD44+CD24− prostate cells that display stem cell characteristics as well as gene expression patterns that predict overall survival in prostate cancer patients. CD44+CD24− cells form colonies in soft agar and form tumours in NOD/SCID mice when as few as 100 cells are injected. Furthermore, CD44+CD24− cells express genes known to be important in stem cell maintenance, such as BMI-1 and Oct-3/4. Moreover, we can maintain CD44+CD24− prostate stem-like cells as nonadherent spheres in serum-replacement media without substantially shifting gene expression. Addition of serum results in adherence to plastic and shifts gene expression patterns to resemble the differentiated parental cells. Thus, we propose that CD44+CD24− prostate cells are stem-like cells responsible for tumour initiation and we provide a genomic definition of these cells and the differentiated cells they give rise to. Furthermore, gene expression patterns of CD44+CD24− cells have a genomic signature that is predictive of poor patient prognosis. Therefore, CD44+CD24− LNCaP prostate cells offer an attractive model system to both explore the biology important to the maintenance and differentiation of prostate cancer stem cells as well as to develop the therapeutics, as the gene expression pattern in these cells is consistent with poor survival in prostate cancer patients.
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