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Molecular Cancer
Published in: Molecular Cancer 1/2006

Open Access 01-12-2006 | Research

Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma

Authors: Gentao Liu, Xiangpeng Yuan, Zhaohui Zeng, Patrizia Tunici, Hiushan Ng, Iman R Abdulkadir, Lizhi Lu, Dwain Irvin, Keith L Black, John S Yu

Published in: Molecular Cancer | Issue 1/2006

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Abstract

Background

Recently, a small population of cancer stem cells in adult and pediatric brain tumors has been identified. Some evidence has suggested that CD133 is a marker for a subset of leukemia and glioblastoma cancer stem cells. Especially, CD133 positive cells isolated from human glioblastoma may initiate tumors and represent novel targets for therapeutics. The gene expression and the drug resistance property of CD133 positive cancer stem cells, however, are still unknown.

Results

In this study, by FACS analysis we determined the percentage of CD133 positive cells in three primary cultured cell lines established from glioblastoma patients 10.2%, 69.7% and 27.5%, respectively. We also determined the average mRNA levels of markers associated with neural precursors. For example, CD90, CD44, CXCR4, Nestin, Msi1 and MELK mRNA on CD133 positive cells increased to 15.6, 5.7, 337.8, 21.4, 84 and 1351 times, respectively, compared to autologous CD133 negative cells derived from cell line No. 66. Additionally, CD133 positive cells express higher levels of BCRP1 and MGMT mRNA, as well as higher mRNA levels of genes that inhibit apoptosis. Furthermore, CD133 positive cells were significantly resistant to chemotherapeutic agents including temozolomide, carboplatin, paclitaxel (Taxol) and etoposide (VP16) compared to autologous CD133 negative cells. Finally, CD133 expression was significantly higher in recurrent GBM tissue obtained from five patients as compared to their respective newly diagnosed tumors.

Conclusion

Our study for the first time provided evidence that CD133 positive cancer stem cells display strong capability on tumor's resistance to chemotherapy. This resistance is probably contributed by the CD133 positive cell with higher expression of on BCRP1 and MGMT, as well as the anti-apoptosis protein and inhibitors of apoptosis protein families. Future treatment should target this small population of CD133 positive cancer stem cells in tumors to improve the survival of brain tumor patients.
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Metadata
Title
Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma
Authors
Gentao Liu
Xiangpeng Yuan
Zhaohui Zeng
Patrizia Tunici
Hiushan Ng
Iman R Abdulkadir
Lizhi Lu
Dwain Irvin
Keith L Black
John S Yu
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2006
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-5-67

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