Neoplastic Human Embryonic Stem Cells as a Model of Radiation Resistance of Human Cancer Stem Cells

Abstract

<p>Recent studies have implicated that a small sub population of cells within a tumour, termed cancer stem cells (CSCs), have an enhanced capacity for tumour formation in multiple cancers and may be responsible for recurrence of the disease after treatment. Further work has suggest that CSCs are radioresistant relative to other cell types composing tumours, in several solid cancers. The genetic and phenotypic heterogeneity of malignant CSCs, as well as the difficulty associated with culturing these cells in vitro, limits the capacity to study the response of CSCs to ionizing radiation. Further, the absence of normal known counterparts for many CSCs has made it difficult to compare the radiation responses of CSCs with the normal stem cells required for post radiotherapy tissue regeneration. Here we have shown that transformed human embryonic stem cells (t-hESCs), showing features of neoplastic progression, produce tumours resistant to radiation relative to their normal counterpart. We further show that t-hESCs have a reduced capacity for radiation induced cell death via apoptosis and exhibit altered cell cycle arrest in vitro, relative to hESCs. We found that decreased levels of p53ser15, following DNA double strand break induction, is associated with this radiation resistance.</p>