Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature

By E. Charafe-Jauffret, Christophe Ginestier, F. Iovino, Julien Wicinski, N. Cervera, P. Finetti, M. Hur, Mark E. Diebel, F. Monville, J. Dutcher and 8 more. Cancer Research, 2009

1,192 citations recorded by the source corpus.

Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have utilized the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize “cancer stem cell” 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 “cancer stem cell” profile that included genes known to play a role in stem cell function as well as genes such as CXCR1/IL8RA not previously known to play such a role. Recombinant IL8 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 cancer stem cells and identify potential stem cell markers and therapeutical targets.

Subfields: Biomedical Engineering, Cancer Research, Oncology

View Paper: https://www.semanticscholar.org/paper/e290d2f504a99be189cb9c838d98609173114584

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biomedical Engineering

1. S. Piccolo
2. S. Dupont

In Cancer Research

1. Aleix Prat
2. S. Piccolo
3. Charles M. Perou
4. S. Baylin
5. M. Wicha
6. Graziano Martello
7. G. Semenza
8. D. Hanahan

In Oncology

1. M. Wicha
2. H. Korkaya
3. Suling Liu
4. Aleix Prat
5. G. Dontu
6. Charles M. Perou
7. Yongheng Chen
8. S. Leonov

Citations in the corpus

• Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks (2011, methodology): “We have previously shown that IL8 interacts with the CXCR1 receptor on CSCs, triggering their self-renewal and invasive properties (14, 30).”
• Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia (2012, background): “Many breast cancer cell lines, includingMDA-MB-231, SUM159, andMCF-7 cells, also contain anAldefluor population that displays stem cell properties in vitro and in NOD/SCID xenografts (12).”
• Targeted drug delivery to tumors: Myths, reality and possibility (2011, neutral): “Even a cultured cell line presents its heterogeneity in cell population including cancer stem-like cells with a different set of surface markers from other bulk cells which can survive from standard cytotoxic treatments [83].”
• Recent advances in therapeutic strategies for triple-negative breast cancer (2022, background): “Cancer stem cells‐related strategies Cancer stem cells (CSCs), which are also known as tumorinitiating cells, have the ability to self-renew to drive the process of tumorgenesis and differentiation, contributing to cancer cells heterogeneity [95].”
• Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA (2016, background): “Only BCSCs are capable of forming a secondary (recurrent or metastatic) tumor (5, 6).”
• A MicroRNA targeting dicer for metastasis control. (2010, background): “…of miR-103/107 in EMT, we found that high versus low levels of pri-miR-103 are associated with mesenchymal versus epithelial phenotypes in a panel of breast cancer cell lines previously stratified according to expression profiles and metastatic capacity (Charafe-Jauffret et al., 2009) (Figure 6I).”
• Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009 (2009, background): “Stem cells Further support for the stem-cell hypothesis in breast cancer arises in preclinical studies in which a subpopulation of cells identified by aldefluor are uniquely capable of transplanting tumours in animal models and appear to have the characteristics of self-renewing stem cells [11].”
• Tumour-initiating cells: challenges and opportunities for anticancer drug discovery (2009, background): “Interestingly, it was observed that, as with primary tumour cells, some cancer cell lines cultured under conventional conditions have a tumour hierarchy based on established tumour-initiating cell marker”
• Deconstructing the molecular portraits of breast cancer (2010, background): “For example, Charafe-Jauffret et al. (2009) reported that many of these cell lines show high expression of ALDH1 and contain functional CSCs.”
• Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases (2017, neutral): “Recent studies suggest that the CXCL8-CXCR1/2 axis may play an important role in the tumor progression and metastasis by regulating CSC proliferation and self-renewal [292, 293, 321, 350-354].”
• Transient Low Doses of DNA Demethylating Agents Exert Durable Anti-tumor Effects on Hematological and Epithelial Tumor Cells (2012, background): “We find, in agreement with others, that the MCF7 breast cancer line has 0.5% ALDH1+ cells (Charafe-Jauffret et al., 2009) and T47Ds contain 5% CD44+/CD24lo (data not shown).”