Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer
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Abstract
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.
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Cancer stem cells exhibit intrinsic resistance to chemotherapy via overexpression of ATP-binding cassette (ABC) drug transporters, enhanced DNA repair capabilities, upregulation of anti-apoptotic proteins, and altered expression of drug metabolism-associated markers.
“CSCs, in particular, exhibit intrinsic resistance to chemotherapy via overexpression of ATP-binding cassette (ABC) drug transporters, enhanced DNA repair capabilities, upregulation of anti-apoptotic proteins, and altered expression of drug metabolism-associated markers [122,123,124].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [122]
The Discussion (“Translational perspectives”; page not provided) reports that prior studies suggested breast cancer stem cells may be relatively resistant to chemotherapy. It does not establish resistance in inflammatory breast cancer or attribute it to ABC transporters, enhanced DNA repair, anti-apoptotic proteins, or altered drug-metabolism markers. (LLM, conf=0.86)
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- Authors
- Charafe-Jauffret, E., Ginestier, C., Iovino, F., Tarpin, C., Diebel, M., Esterni, B., Houvenaeghel, G., Extra, J.-M., Bertucci, F., Jacquemier, J., Xerri, L., Dontu, G., Stassi, G., Xiao, Y., Barsky, S. H., Birnbaum, D., Viens, P., & Wicha, M. S.
- Affiliations
- Authors' Affiliations: 1Marseille Cancer Research Center, Department of Molecular Oncology and 2Department of Biopathology, Institut Paoli-Calmettes/UMR891 Institut National de la Sante et de la Recherche Medicale, 3Université de la Méditerranée, and Departments of 4Oncology and 5Biostatistics, UMR891 Institut Paoli-Calmettes/Institut National de la Sante et de la Recherche Medicale, Marseille, France; 6Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan; 7Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy; and 8Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio
- Inserm (FR)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2010-01-01
- Volume
- 16
- Issue
- 1
- Pages
- 45-55
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2874875
- OpenAlex
- W2105504936
- Cited by
- 732
- References
- 45
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 22 · 2023: 25 · 2022: 24 · 2021: 32 · 2020: 48 · 2019: 40 · 2018: 35 · 2017: 61 · 2016: 56 · 2015: 63 · 2014: 73 · 2013: 62 · 2012: 69
- FWCI
- 27.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- China Scholarship Council
- National Cancer Institute (CA101860, CA29765, P36CA45692, R01CA101860)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- inflammatory breast cancer, cancer stem cells, ALDH1, metastasis, prognostic factors, patient survival, tumor invasion, ALDEFLUOR assay
- MeSH terms
- Aldehyde Dehydrogenase 1 Family, Aldehyde Dehydrogenase, Animals, Breast Neoplasms, Female, Humans, Inflammation, Isoenzymes, Neoplasm Metastasis, Neoplasm Transplantation, Biomarkers, Tumor, Neoplastic Stem Cells, Mice, SCID, Mice, Inbred NOD, Treatment Outcome, Cell Line, Tumor, Retinal Dehydrogenase, Mice
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