Overexpression of CD133 promotes drug resistance in C6 glioma cells.
Glioblastoma multiforme is an extremely aggressive and clinically unresponsive form of cancer. Transformed neoplastic neural stem cells, resistant to chemotherapy and radiation therapy, are thought to be responsible for the initial tumor formation and the recurrence of disease following surgical resection. These stem cells express multidrug resistance markers along with CD133. We show that ectopic overexpression of CD133 in rat C6 glioma cells leads to significant reluctance to undergo apoptosis from camptothecin and doxorubicin. Although p53 was upregulated in CD133-overexpressing glioma cells treated with DNA-damaging agents, apoptosis seems to be p53 independent. At least one ABC transporter, rat P-glycoprotein/ABCB1, was upregulated by 62% in CD133(+) cells with a corresponding increase in activity. Thus, the combination of higher P-glycoprotein mRNA transcription and elevated transporter activity seems to contribute to the protection from cytotoxic reagents. In conclusion, previous investigators have reported that resilient cancer stem cells coexpress CD133 and ABC transporters with increased reluctance toward apoptosis. Our data suggest that CD133 may contribute to the observed resistance to apoptosis of CD133(+) cancer stem cells.
Angelastro
James M
JM
Department of Molecular Biosciences, University of California, Davis, CA 95616, USA. jmangelastro@ucdavis.edu
Lamé
Michael W
MW
D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; C494828:Bax protein, rat; D006023:Glycoproteins; D010455:Peptides; C000606025:Prom1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; D002166:Camptothecin