Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy

By Christine M. Fillmore, Charlotte Kuperwasser. Breast Cancer Research, 2008

1,091 citations recorded by the source corpus.

IntroductionThe phenotypic and functional differences between cells that initiate human breast tumors (cancer stem cells) and those that comprise the tumor bulk are difficult to study using only primary tumor tissue. We embarked on this study hypothesizing that breast cancer cell lines would contain analogous hierarchical differentiation programs to those found in primary breast tumors.MethodsEight human breast cell lines (human mammary epithelial cells, and MCF10A, MCF7, SUM149, SUM159, SUM1315 and MDA.MB.231 cells) were analyzed using flow cytometry for CD44, CD24, and epithelial-specific antigen (ESA) expression. Limiting dilution orthotopic injections were used to evaluate tumor initiation, while serial colony-forming unit, reconstitution and tumorsphere assays were performed to assess self-renewal and differentiation. Pulse-chase bromodeoxyuridine (5-bromo-2-deoxyuridine [BrdU]) labeling was used to examine cell cycle and label-retention of cancer stem cells. Cells were treated with paclitaxol and 5-fluorouracil to test selective resistance to chemotherapy, and gene expression profile after chemotherapy were examined.ResultsThe percentage of CD44+/CD24- cells within cell lines does not correlate with tumorigenicity, but as few as 100 cells can form tumors when sorted for CD44+/CD24-/low/ESA+. Furthermore, CD44+/CD24-/ESA+ cells can self-renew, reconstitute the parental cell line, retain BrdU label, and preferentially survive chemotherapy.ConclusionThese data validate the use of cancer cell lines as models for the development and testing of novel therapeutics aimed at eradicating cancer stem cells.

Subfields: Immunology, Oncology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/cea924d946eefa9972121438313459f92ef8a246

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Citations in the corpus

Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast (2011, methodology): “As a surrogate assay for tumor-initiating ability, we tested the formation of tumorspheres in three-dimensional cultures at clonal densities (Fillmore and Kuperwasser, 2008).”
Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis (2015, background): “Collectively, these studies show that CD44 + /CD24 expression does not necessarily correlates with tumorigenicity (160), and consolidate the mounting evidence that cells with a biphenotypic E/M expression tend to have high tumorigenicity in mice (156,161–163).”
Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state (2011, background): “The CSC phenotype of the different CD44 cell populations was assessed in vitro by assessing tumorsphere-forming ability, where only CSC-derived tumorspheres have the ability to be serially passaged (11, 24).”
Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature (2009, neutral): “In addition, cell surface markers defined using primary tumor xenografts, such as CD44 and CD133, have also been used to identify similar populations in established cell lines (7, 8).”
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”
Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. (2011, neutral): “Characterization of Luminal, Basal, and Stem-like Differentiation States in Breast Cancer Cells To study cell-state dynamics in cancer cells, we used fluorescence-activated cell sorting (FACS) to isolate three mammary epithelial cell states that have been previously defined and characterized using c”
Identification of selective inhibitors of cancer stem cells by high-throughput screening (2009, background): “For example, breast CSC enrichment is rapidly lost during in vitro culture (Fillmore and Kuperwasser, 2008).”
Choosing the right cell line for breast cancer research (2011, background): “Increasingly demonstrated is that very small numbers of CSCs (often described as tumour-initiating cells) exist within human breast cancer cell lines [31,32].”
Poised chromatin at the ZEB1 promoter enables cell plasticity and enhances tumorigenicity (2013, neutral): “Among these antigens, it is widely accepted that breast CSCs are contained exclusively in the CD44hi cell compartment (Al-Hajj et al., 2003; Fillmore and Kuperwasser, 2008; Mani et al., 2008; Visvader and Lindeman, 2012).”
Deconstructing the molecular portraits of breast cancer (2010, background): “This is in concordance with two other reports (Fillmore and Kuperwasser, 2008; Sheridan et al., 2006) that showed that the MDA-MB231, SUM159PT, SUM1315 MDA-MB436, Hs578T and HBL100 cell lines have a high proportion (>90”