Etiology and Pathogenesis > Cancer Stem Cells

Abstract

Gentao Liu^1 ,2, Xiangpeng Yuan¹, Zhaohui Zeng¹, Patrizia Tunici¹, Hiushan Ng¹, Iman R Abdulkadir¹, Lizhi Lu^1 ,3, Dwain Irvin¹, Keith L Black¹ and John S Yu^{1 ,4, *}

¹Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. ²Division of Hematology/Oncology, Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA, Los Angeles, CA, 90048, USA. ³Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, P.R. China. ⁴8631 West Third Street, Suite 800E, Los Angeles, CA, 90048, USA. -- *Corresponding Author. Email: yuj@cshs.org -- Received: 19 June 2006, Accepted: 2 December 2006, Published: 2 December 2006

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.