Ablation of Breast Cancer Stem Cells with Radiation

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Translational oncology (Impact Factor: 2.88). 08/2011; 4(4):227-33. DOI: 10.1593/tlo.10247
Source: PubMed


Tumor radioresistance leads to recurrence after radiation therapy. The radioresistant phenotype has been hypothesized to reside in the cancer stem cell (CSC) component of breast and other tumors and is considered to be an inherent property of CSC. In this study, we assessed the radiation resistance of breast CSCs using early passaged, patient-derived xenografts from two separate patients. We found a patient-derived tumor in which the CSC population was rapidly depleted 2 weeks after treatment with radiation, based on CD44(+) CD24(-) lin(-) phenotype and aldehyde dehydrogenase 1 immunofluorescence, suggesting sensitivity to radiotherapy. The reduction in CSCs according to phenotypic markers was accompanied by a decrease in functional CSC activity measured by tumor sphere frequency and the ability to form tumors in mice. In contrast, another patient tumor sample displayed enrichment of CSC after irradiation, signifying radioresistance, in agreement with others. CSC response to radiation did not correlate with the level of reactive oxygen species in CSC versus non-CSC. These findings demonstrate that not all breast tumor CSCs are radioresistant and suggest a mechanism for the observed variability in breast cancer local recurrence.

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Available from: Steven Zielske, Mar 21, 2014
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    • "CSCs from one patients were rapidly depleted 2 weeks after treatment with radiation, resulting in a significant decrease in tumor sphere frequency and tumorigenic capacity. In contrast, CSCs from the other patient showed enrichment after radiation and resistance to therapy, suggesting that CSC variance may exist in individual patients [56] . Therefore, therapeutics that target different CSC subtypes is likely required. "
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    • "Consistent with this finding, knockdown of CD44 expression has been found to induce breast CSCs to differentiate into regular tumor cells without the capacity to self-renew (defined as non-CSCs) [13]. Nevertheless, in certain breast cancer patients, CD44+/CD24- cells are still sensitive to radiotherapy, suggesting that not all breast CSCs are radioresistant [14] and that not all CD44+/CD24- cells are CSCs. Indeed, clinical data have indicated that there is no significant correlation between CD44+/CD24-/low tumor cell prevalence and tumor progression. "
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