Ablation of Breast Cancer Stem Cells with Radiation

Abstract

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.

Nanog signaling in cancer promotes stem-like phenotype and immune evasion

“…CSCs are commonly spared and thus enriched by conventional forms of cancer therapy, such as radiation or pharmacologic agents (22)(23)(24)(25). However, the relationship between CSCs and the host immune system is largely unknown.…”

The changing paradigm of tumour response to irradiation

“…However, a higher intrinsic radioresistance of CSC cannot be regarded as a general phenomenon, since heterogeneity seems to exist between individual tumours of the same histology. 82 A link between hypoxia and putative stem cells has also been shown by an increase in the fraction of CD133 1 cells in brain tumour cells exposed to hypoxia in vitro, 83,84 and the preferential expression of hypoxia induced factor (HIF)-2a-and HIF-regulated genes in glioma stem cells. 85 Specific microenvironmental factors such as cellcell interactions and genetically regulated cellular signals may also be important determinants for stem cell maintenance and survival.…”

Screening specific polypeptides of breast cancer stem cells from a phage display random peptide library

“…A number of experiments and studies have been conducted on cancer stem cells. Based on the existing stem cell separation technology, the association between breast cancer stem cells and viruses, expression of estrogen and radiation treatment have been studied (7)(8)(9). In 2012, three separate teams of researchers used genetic marker technology to track cell proliferation, particularly cancer cell growth, which provided strong evidence to confirm the existence of cancer stem cells (10)(11)(12).…”