Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.
Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.
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DOI：
10.1158/0008-5472.can-08-2741
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发表时间：
2009-02-15
期刊：
影响因子：
11.2
通讯作者：
Wicha MS
中科院分区：
文献类型：
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作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
肿瘤可能由具有干细胞特性的细胞亚群引发并维持。我们利用ALDEFLUOR检测所评估的醛脱氢酶的表达，在源自正常和恶性乳腺组织的33个细胞系中分离并鉴定“癌症干细胞”群体。33个细胞系中有23个包含ALDEFLUOR阳性群体，该群体在体外以及在NOD/SCID异种移植物中显示出干细胞特性。基因表达谱分析确定了一个413个基因的“癌症干细胞”谱，其中包括已知在干细胞功能中起作用的基因，以及诸如CXCR1/IL8RA等此前未知具有此类作用的基因。重组IL8增加了乳腺癌细胞系中乳腺球的形成以及ALDEFLUOR阳性群体。最后，我们表明ALDEFLUOR阳性细胞负责介导转移。这些研究证实了永生化细胞系的层级结构，建立了有助于癌症干细胞调控通路特征描述的技术，并确定了潜在的干细胞标志物和治疗靶点。
Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have utilized the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize “cancer stem cell” populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene “cancer stem cell” profile that included genes known to play a role in stem cell function as well as genes such as CXCR1/IL8RA not previously known to play such a role. Recombinant IL8 increased mammosphere formation and the ALDEFLUOR-positive population in breast cancer cell lines. Finally, we show that ALDEFLUOR-positive cells are responsible for mediating metastasis. These studies confirm the hierarchical organization of immortalized cell lines, establish techniques that can facilitate the characterization of regulatory pathways of cancer stem cells and identify potential stem cell markers and therapeutical targets.