Involvement of CD133+ stem cells in the chemoresistance of glioma

Abstract

Despite aggressive treatment strategies, malignant gliomas frequently recur and the median survival remains approximately one year for these patients. Within a heterogeneous brain tumour mass, there is a subpopulation of cancer stem cells that possess the capacity for selfrenewal, infinite proliferative potential and multipotency. The novel cell-membrane protein
CD133 has been identified as a marker of stem-like cells in glioma. Interestingly, the CDI 33+ population of GBM has been found to be selectively resistant to radiation and chemotherapy relative to the CD133- bulk tumour mass, revealing a potential source for the inevitable recurrence of this disease.
In the current study, the U87MG and 1321N1 glioma cell lines were cultured in serum containing medium (SCM) and serum free medium (SFM). In SFM, the U87MG cells grew as neurospheres suggesting the presence of stem cells in this cell line while in the 1321N1 cells no neurospheres were observed. Immunocytochemistry and fluorescence-activated cell
sorting (FACS) analysis revealed the absence of CD133+ cells in 1321N1 cell line in both SCM and SFM. The U87MG cells did not express detectable levels of CD 133 in SCM but revealed the presence of 1.2% of CD133+ cells in SFM. To establish a link between chemoresistance and cancer stem cells, the glioma cell lines were treated with commercially available anti-cancer drugs at various concentrations and their chemosensitivity was compared in SFM and SCM. The U87MG cells when treated with cisplatin were significantly (P<0.05) less chemosensitive in SFM than in SCM. However, the cell survii'al in the two culture conditions did not vary significantly (P>0.05) when treated with temozolomide (TMZ). This indicates that the enriched stem cell population of U87MG cells in the SFM are chemosensitive to TMZ. The 1321N1 cell line did not show any significant difference (P>0.05) in the chemosensitivity in SCM and SFM when treated with either cisplatin or TMZ.
In conclusion, the hypothesis that CD133+ stem cells are present in the glioma cell lines is in agreement with the results of only the U87MG cells in the SFM but not with the 1321N1 cell line. Also, CD 133 is not expressed by all the cancer stem cells nor is it expressed by all cell lines indicating the need for more specific markers for the identification of cancer stem cells
in glioma. Interestingly, the hypothesis that CD133+ stem cells contribute to chemoresistance is in agreement with the data showing that the enriched stem cell population in SFM in the U87MG cell line is significantly chemoresistant to cisplatin, but is not the case with TMZ.