title: Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer.
abstract: OBJECTIVE
  To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer.
  
  
  METHODS
  CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank tests using Kaplan-Meier analysis were used to determine the correlation of ALDH1 expression with development of metastasis and patient outcome.
  
  
  RESULTS
  Both in vitro and xenograft assays showed that invasion and metastasis in IBC are mediated by a cellular component that displays ALDH activity. Furthermore, expression of ALDH1 in IBC was an independent predictive factor for early metastasis and decreased survival in this patient population.
  
  
  CONCLUSIONS
  These results suggest that the metastatic, aggressive behavior of IBC may be mediated by a CSC component that displays ALDH enzymatic activity. ALDH1 expression represents the first independent prognostic marker to predict metastasis and poor patient outcome in IBC. The results illustrate how stem cell research can translate into clinical practice in the IBC field.
authors.affiliation: Department of Molecular Oncology, Institut Paoli-Calmettes/UMR891 Institut National de la Sante et de la Recherche Medicale, Université de la Méditerranée, Marseille Cancer Research Center, Marseille, France. jauffrete@marseille.fnclcc.fr
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Flora
authors.initials: F
authors.lastname: Iovino
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.forename: Mark
authors.initials: M
authors.lastname: Diebel
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Gilles
authors.initials: G
authors.lastname: Houvenaeghel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Gabriela
authors.initials: G
authors.lastname: Dontu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Sanford H
authors.initials: SH
authors.lastname: Barsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D050697:Retinal Dehydrogenase; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase