Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.

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.

• Authors: Emmanuelle Charafe-Jauffret, Christophe Ginestier, Flora Iovino, Julien Wicinski, Nathalie Cervera, Pascal Finetti, Min-Hee Hur, Mark E Diebel, Florence Monville, Julie Dutcher, Marty Brown, Patrice Viens, Luc Xerri, François Bertucci, Giorgio Stassi, Gabriela Dontu, Daniel Birnbaum, Max S Wicha
• Journal: Cancer research (Cancer Res) Vol. 69 Issue 4 Pg. 1302-13 (Feb 15 2009) ISSN: 1538-7445 [Electronic] United States
• PMID: 19190339 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• RNA, Neoplasm
• Receptors, Interleukin-8A
• Aldehyde Dehydrogenase

Topics

• Aldehyde Dehydrogenase (genetics)
• Animals
• Biomarkers, Tumor (metabolism)
• Breast (cytology)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Line
• Cell Line, Tumor
• Female
• Flow Cytometry
• Gene Expression Profiling
• Homeostasis
• Humans
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Neoplasm Metastasis (pathology)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics, isolation & purification)
• Receptors, Interleukin-8A (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cells (cytology, pathology, physiology)