Forced extinction of CD24 stem-like breast cancer marker alone promotes radiation resistance through the control of oxidative stress

Mol Carcinog. 2016 Mar;55(3):245-54. doi: 10.1002/mc.22273. Epub 2015 Jan 16.

Abstract

Along with CD44, CD24 is a key marker of breast cancer stem cells (CSCs), frequently defined by CD24(-)/CD44(+) labeling. Among all phenotypes classically attributed to breast CD24(-)/CD44(+) cancer cells, radiation resistance has been extensively described and seen as being implicated in radiotherapy failure. Our previous data indicated that CD24(-) cells constitute a radiation-resistant subpopulation transitory selected by high doses of ionizing radiation. However, little is known about the biological role of CD24 in breast cancers, and no function has been assigned to CD24 in radiation response. Here, CD24 expression was induced in CD24(-) cells or knocked-down in CD24(+) cells. We show that forced extinction of CD24 expression is associated with decreased proliferation rate, lower levels of reactive oxygen species (ROS) and decreased genomic instability. On the opposite when CD24 is artificially expressed in CD24(-) cells, proliferation rates in vitro and in vivo, ROS levels and genomic instability are enhanced. Moreover, we observe that loss of CD24 expression leads to radiation resistance, by preventing radiation-induced cell death and promoting generation of progeny in relation to lower G2/M blockade and a smaller proportion of polyploid cells. Finally, control of ROS levels appears to be the key event in the CD24-mediated radiation response. For the first time, CD24 is proposed as a direct actor in radiation response of breast cancer cells, independently of CD44 expression. These findings could have interesting applications in evaluating the intrinsic radiation response of primary tumors.

Keywords: CD24; breast cancer; genomic instability; irradiation; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast / metabolism
  • Breast / pathology
  • Breast / radiation effects*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • CD24 Antigen / analysis
  • CD24 Antigen / genetics*
  • Cell Line, Tumor
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Humans
  • Hyaluronan Receptors / analysis
  • Hyaluronan Receptors / genetics
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects
  • Oxidative Stress*

Substances

  • CD24 Antigen
  • Hyaluronan Receptors