Tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma

Stem Cells Dev. 2007 Oct;16(5):837-47. doi: 10.1089/scd.2007.0006.

Abstract

Glioblastoma multiforme (GBM) is the most frequently occurring brain cancer. Although the existence of cancer stem cells (CSCs) in GBM has been established, there is little evidence to explain the link between CSCs and chemoresistance. In this study, we developed a dissociated cell system of human GBM cells, A172 and established GBM2 cells, that have shown resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). After exposure to a lethal dose of BCNU, the small population of GBM cancer cells survived and proliferated, as opposed to direct inhibition of the apoptosis and activation of the proliferation signal. Also, these cells contained subpopulations of stem-like cells, expressing CD133, CD117, CD90, CD71, and CD45 cell-surface markers, and had the capacity for multipotency. Moreover, we observed that BCNU-resistant subpopulations derived from GBM cancer cells can be grown to tumors when transplanted into severe combined immunodeficient (SCID) mouse brain. These results demonstrated that BCNU-resistant subpopulations derived from GBM have cancer stem-like cell properties. These findings provide further evidence that CSCs in GBM display chemotherapeutic drug resistance. Hopefully, it will be possible to improve the therapeutic outcome of GBM, leading to better anticancer strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / pathology*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Separation
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm*
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, SCID
  • Microscopy, Confocal
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / pathology
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor