High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population

Exp Cell Res. 2007 May 15;313(9):1877-85. doi: 10.1016/j.yexcr.2007.03.006. Epub 2007 Mar 15.

Abstract

Cancer stem cells are supposed to be resistant to apoptosis, but information for this is quite limited. Cancer stem cells are usually isolated as dye-effluxing cells with Hoechst 33342 staining, called side-population (SP) cells. Because Hoechst 33342 dye itself induces apoptosis, the SP cells isolated by such method are not suitable for evaluation of apoptosis. For accurate assessment, SP cells must be isolated without Hoechst 33342. Here, we found that CD55 was highly expressed in SP cells of two mammary gland carcinoma cell lines. Then, the high expression of CD55 was used for isolation of cancer stem cells among mammary carcinoma cell lines as a surrogate character. Cells expressing high level of CD55 (CD55(hi)) were resistant to apoptosis induced by serum depletion as in the case of SP cells. In ceramide-inducing apoptosis, CD55(hi) cells showed high tolerance. Anti-apoptotic molecules such as Bcl-2 were abundantly expressed in both SP cells and CD55(hi) cells. These findings indicated that SP cells as revealed to be CD55(hi) cells were tolerant to apoptosis. The high expression of CD55 may be a useful character for SP cells in evaluating their functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism
  • Benzimidazoles
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / immunology*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism
  • CD55 Antigens / biosynthesis*
  • CD55 Antigens / immunology
  • Carcinoma / diagnosis
  • Carcinoma / immunology
  • Carcinoma / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Separation / methods*
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism*
  • Ceramides / pharmacology
  • Culture Media, Serum-Free / pharmacology
  • Humans
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Stem Cells / cytology
  • Stem Cells / immunology
  • Stem Cells / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Benzimidazoles
  • Biomarkers, Tumor
  • CD55 Antigens
  • Ceramides
  • Culture Media, Serum-Free
  • bisbenzimide ethoxide trihydrochloride