Breast Cancer Cell Lines Contain Functional Cancer Stem Cells with Metastatic Capacity and a Distinct Molecular Signature

被引：974

作者：

Charafe-Jauffret, Emmanuelle ^{[2
]}

Ginestier, Christophe ^{[1
]}

Iovino, Flora ^{[3
]}

Wicinski, Julien ^{[2
]}

Cervera, Nathalie ^{[2
]}

Finetti, Pascal ^{[2
]}

Hur, Min-Hee ^{[4
]}

Diebel, Mark E. ^{[1
]}

Monville, Florence ^{[2
]}

Dutcher, Julie ^{[1
]}

Brown, Marty ^{[1
]}

Viens, Patrice ^{[2
]}

Xerri, Luc ^{[2
]}

Bertucci, Francois ^{[2
]}

Stassi, Giorgio ^{[3
]}

Dontu, Gabriela ^{[1
]}

Birnbaum, Daniel ^{[2
]}

Wicha, Max S. ^{[1
]}

机构：

[1] Univ Michigan, Ctr Comprehens Canc, Dept Internal Med Oncol, Ann Arbor, MI 48109 USA

[2] Univ Aix Marseille 2, INSERM, Inst Paoli Calmettes, Ctr Rech Cancerol Marseille,UMR891,Lab Oncol Mol, Marseille, France

[3] Univ Palermo, Dept Surg & Oncol Sci, Cellular & Mol Pathophysiol Lab, Palermo, Italy

[4] Sungkyunkwan Univ, Cheil Gen Hosp, Seoul, South Korea

来源：

CANCER RESEARCH | 2009年 / 69卷 / 04期

关键词：

ALDEHYDE DEHYDROGENASE-ACTIVITY; ACUTE MYELOID-LEUKEMIA; IN-VITRO PROPAGATION; PROSTATE-CANCER; SIDE POPULATION; EXPRESSION; TUMORIGENICITY; IDENTIFICATION; INTERLEUKIN-8; CARCINOMA;

D O I：

10.1158/0008-5472.CAN-08-2741

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) 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 CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant interleukin-8 (IL-8) 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 CSCs, and identify potential stem cell markers and therapeutic targets. [Cancer Res 2009;69(4):1302-13]

引用

页码：1302 / 1313

页数：12

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[1]

Prospective identification of tumorigenic breast cancer cells [J].