Abstract
The cancer stem cell (CSC) model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation–induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.
Highlights
Cancer stem cells (CSCs), a subpopulation of malignant cells in the heterogeneous cancer cell population, are considered to be responsible for cancer recurrence, metastasis and drug resistance
We first examined the effect of ionizing radiation on the ability of hepatocellular carcinoma cells, for which a CSC component has been previously described [6,32], to grow as spheres under stem cell media (SCM) culture conditions
CSCs are believed to play a key role in cancer metastasis, cancer recurrence, and cancer drug resistance [15,20,44,45]
Summary
Cancer stem cells (CSCs), a subpopulation of malignant cells in the heterogeneous cancer cell population, are considered to be responsible for cancer recurrence, metastasis and drug resistance. Studies published by Bao et al [20] have demonstrated that ionizing radiation can enrich CD133+ glioma cancer stem cells in vitro and in vivo. These authors showed that this enrichment effect was mediated by preferential activation of the DNA damage checkpoint in CD133+ glioma cancer stem cells compared to CD133- non-stem glioma cells. The CSC model, calls for the design of therapeutics that target CSCs to improve cancer treatment [21,22]
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