Aldehyde Dehydrogenase 1–Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer

• Published in: Clinical cancer research 2010-01, Vol.16 (1), p.45-55
• Main Authors: CHARAFE-JAUFFRET, Emmanuelle, GINESTIER, Christophe, XERRI, Luc, DONTU, Gabriela, STASSI, Giorgio, YI XIAO, BARSKY, Sanford H, BIRNBAUM, Daniel, VIENS, Patrice, WICHA, Max S, IOVINO, Flora, TARPIN, Carole, DIEBEL, Mark, ESTERNI, Benjamin, HOUVENAEGHEL, Gilles, EXTRA, Jean-Marc, BERTUCCI, François, JACQUEMIER, Jocelyne
• Format: Article
• Language: English
• Subjects: Aldehyde dehydrogenase; Aldehyde Dehydrogenase - metabolism; Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - metabolism; Breast Neoplasms - enzymology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Cell Line, Tumor; Cellular Biology; Female; Gynecology. Andrology. Obstetrics; Humans; Inflammation - enzymology; Inflammatory breast carcinoma; Isoenzymes - metabolism; Life Sciences; Mammary gland diseases; MARY-X; Medical sciences; Metastasis; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Stem Cells - enzymology; Pharmacology. Drug treatments; Retinal Dehydrogenase; Stem cell; SUM149; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1630

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. Clin Cancer Res; 16(1); 45–55