Ionizing radiation induces stemness in cancer cells

PLoS One. 2012;7(8):e43628. doi: 10.1371/journal.pone.0043628. Epub 2012 Aug 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gamma Rays*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / radiation effects*
  • Octamer Transcription Factor-3 / deficiency
  • Octamer Transcription Factor-3 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • SOXB1 Transcription Factors / deficiency
  • SOXB1 Transcription Factors / genetics

Substances

  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Messenger
  • SOX2 protein, human
  • SOXB1 Transcription Factors

Grant support

This study was supported by Skip Ackerman Center for Molecular Therapeutics Fund and Global Research Laboratory Award (Ministry of Education Science and Technology, Korea). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.