Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.
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.
Charafe-Jauffret
Emmanuelle
E
Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France.
Ginestier
Christophe
C
Iovino
Flora
F
Wicinski
Julien
J
Cervera
Nathalie
N
Finetti
Pascal
P
Hur
Min-Hee
MH
Diebel
Mark E
ME
Monville
Florence
F
Dutcher
Julie
J
Brown
Marty
M
Viens
Patrice
P
Xerri
Luc
L
Bertucci
François
F
Stassi
Giorgio
G
Dontu
Gabriela
G
Birnbaum
Daniel
D
Wicha
Max S
MS
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D023062:Receptors, Interleukin-8A / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000473:pathology* / Q000502:physiology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D023062:Receptors, Interleukin-8A; D000444:Aldehyde Dehydrogenase