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

¹Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France; ²Comprehensive Cancer Center, Department of Internal Medicine/Oncology, University of Michigan, Ann Arbor, Michigan; ³Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy; and ⁴Cheil General Hospital, Sungkyunkwan University, Seoul, Republic of Korea

^* To whom correspondence should be addressed. E-mail: mwicha{at}med.umich.edu.

	Abstract

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]

Key Words: cancer stem cells, cell line, IL-8, breast cancer, metastasis

This article has been cited by other articles:

				A. Goldhirsch, J. N. Ingle, R. D. Gelber, A. S. Coates, B. Thurlimann, H.-J. Senn, and Panel members Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009 Ann. Onc., August 1, 2009; 20(8): 1319 - 1329. [Abstract] [Full Text] [PDF]

				J. J. Short and D. T. Curiel Oncolytic adenoviruses targeted to cancer stem cells Mol. Cancer Ther., August 1, 2009; 8(8): 2096 - 2102. [Abstract] [Full Text] [PDF]

				D. S. Schrump Cytotoxicity Mediated by Histone Deacetylase Inhibitors in Cancer Cells: Mechanisms and Potential Clinical Implications Clin. Cancer Res., June 15, 2009; 15(12): 3947 - 3957. [Abstract] [Full Text] [PDF]