PTEN status is related to cell proliferation and self-renewal independent of CD133 phenotype in the glioma-initiating cells.
CD133 is extensively used as a surface marker to identify and isolate glioma-initiating cells (GICs) from malignant brain tumors; however, instances of CD133(-) cells exhibiting similar properties have also been reported. To clarify the availability of CD133 as the GIC marker, we first evaluated the ratio of CD133(+) cells and malignancy of glioma spheroids GIC1 and GIC2, respectively. GIC1, which showed a lower percentage of CD133(+) cells, exhibited a highly aggressive behavior in comparison with GIC2. The following experiments demonstrated that tumor suppressor PTEN was lost in GIC1, resulting in the activation of AKT pathway. Overexpression of recombinant PTEN in GIC1 suppressed its proliferation and self-renew without significant effect on CD133 expression level, indicating that the inconsistence between the ratio of CD133(+) cells and proliferation and self-renewal capacity of GIC1 and GIC2 was caused by PTEN deficiency. To further validate our conclusion, a series of GICs were analyzed and the percentages of CD133(+) cells could not reflect the degrees of cell proliferation and self-renewal characteristics in the PTEN deficient GICs, suggesting that the application of CD133 as the GIC maker was restricted by PTEN loss. Furthermore, down-regulation of PTEN in the PTEN-expressing GICs could break the positive correlation between the ratio of CD133(+) cells and proliferation and self-renewal capacity. Our results demonstrated that PTEN status is related to cell proliferation and self-renewal independent of CD133 phenotype in the glioma-initiating cells, resulting in the limitations of CD133 as a biomarker for PTEN deficient GICs.
Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, People's Republic of China. biothcheng@hotmail.com
Ru-Bin
RB
Cheng
Rui-Juan
RJ
Ma
Zhao-Kai
ZK
Wang
Shan-Jun
SJ
Yang
Xiang-Zhi
XZ
Lin
Hui
H
Rong
Yong
Y
Ma
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D047368:Tumor Burden / Q000235:genetics; D014407:Tumor Cells, Cultured
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human