Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content
Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content
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DOI：
10.1016/j.cell.2009.12.007
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发表时间：
2010-01-08
期刊：
影响因子：
64.5
通讯作者：
Di Fiore, Pier Paolo
中科院分区：
文献类型：
--
作者：
Pece, Salvatore;Tosoni, Daniela;Di Fiore, Pier Paolo
控制干细胞（SC）功能的途径通常在癌症中被破坏。在这里，我们报告的分离，以接近纯度的人正常乳腺干细胞（hNMSC），从培养的mammospheres，其能力的基础上，保留亲脂性染料PKH26作为其静态性质的结果。PKH26阳性细胞具有hNMSCs的所有特征。PKH26阳性细胞的转录谱（hNMSC签名）能够预测乳腺癌的生物学和分子特征。通过使用hNMSC签名的标记物，我们前瞻性地从正常腺体和乳腺肿瘤中分离SC。低分化（G3）癌症显示出比高分化（G1）癌症更高的前瞻性分离的癌症干细胞（CSC）含量。通过在异种移植实验中比较G3和G1肿瘤，我们直接证明了G3在CSC中富集。我们的数据支持这一观点，即人类乳腺癌的异质性表型和分子特征是其CSC含量的函数。
Pathways that govern stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SCs (hNMSCs), from cultured mammospheres, on the basis of their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we prospectively isolated SCs from the normal gland and from breast tumors. Poorly differentiated (G3) cancers displayed higher content of prospectively isolated cancer SCs (CSCs) than did well-differentiated (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in CSCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their CSC content.