PMID- 20028757 OWN - NLM STAT- MEDLINE DCOM- 20100416 LR - 20220408 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 16 IP - 1 DP - 2010 Jan 1 TI - Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. PG - 45-55 LID - 10.1158/1078-0432.CCR-09-1630 [doi] AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. FAU - Charafe-Jauffret, Emmanuelle AU - Charafe-Jauffret E AD - Department of Molecular Oncology, Institut Paoli-Calmettes/UMR891 Institut National de la Sante et de la Recherche Medicale, Universite de la Mediterranee, Marseille Cancer Research Center, Marseille, France. jauffrete@marseille.fnclcc.fr FAU - Ginestier, Christophe AU - Ginestier C FAU - Iovino, Flora AU - Iovino F FAU - Tarpin, Carole AU - Tarpin C FAU - Diebel, Mark AU - Diebel M FAU - Esterni, Benjamin AU - Esterni B FAU - Houvenaeghel, Gilles AU - Houvenaeghel G FAU - Extra, Jean-Marc AU - Extra JM FAU - Bertucci, Francois AU - Bertucci F FAU - Jacquemier, Jocelyne AU - Jacquemier J FAU - Xerri, Luc AU - Xerri L FAU - Dontu, Gabriela AU - Dontu G FAU - Stassi, Giorgio AU - Stassi G FAU - Xiao, Yi AU - Xiao Y FAU - Barsky, Sanford H AU - Barsky SH FAU - Birnbaum, Daniel AU - Birnbaum D FAU - Viens, Patrice AU - Viens P FAU - Wicha, Max S AU - Wicha MS LA - eng GR - P36CA45692/CA/NCI NIH HHS/United States GR - R01 CA101860-06/CA/NCI NIH HHS/United States GR - CA29765/CA/NCI NIH HHS/United States GR - R01 CA101860/CA/NCI NIH HHS/United States GR - CA101860/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20091222 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Biomarkers, Tumor) RN - 0 (Isoenzymes) RN - EC 1.2.1 (Aldehyde Dehydrogenase 1 Family) RN - EC 1.2.1.3 (Aldehyde Dehydrogenase) RN - EC 1.2.1.36 (ALDH1A1 protein, human) RN - EC 1.2.1.36 (ALDH1A1 protein, mouse) RN - EC 1.2.1.36 (Retinal Dehydrogenase) SB - IM MH - Aldehyde Dehydrogenase/*metabolism MH - Aldehyde Dehydrogenase 1 Family MH - Animals MH - Biomarkers, Tumor/metabolism MH - Breast Neoplasms/*enzymology/mortality/pathology MH - Cell Line, Tumor MH - Female MH - Humans MH - Inflammation/*enzymology MH - Isoenzymes/*metabolism MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - *Neoplasm Metastasis MH - Neoplasm Transplantation MH - Neoplastic Stem Cells/*enzymology MH - Retinal Dehydrogenase MH - Treatment Outcome PMC - PMC2874875 MID - NIHMS200775 EDAT- 2009/12/24 06:00 MHDA- 2010/04/17 06:00 PMCR- 2011/01/01 CRDT- 2009/12/24 06:00 PHST- 2009/12/24 06:00 [entrez] PHST- 2009/12/24 06:00 [pubmed] PHST- 2010/04/17 06:00 [medline] PHST- 2011/01/01 00:00 [pmc-release] AID - 1078-0432.CCR-09-1630 [pii] AID - 10.1158/1078-0432.CCR-09-1630 [doi] PST - ppublish SO - Clin Cancer Res. 2010 Jan 1;16(1):45-55. doi: 10.1158/1078-0432.CCR-09-1630. Epub 2009 Dec 22.