Overexpression of CD133 promotes drug resistance in C6 glioma cells

James M Angelastro, Michael W. Lamé

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1105-1115
Number of pages11
JournalMolecular Cancer Research
Volume8
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Drug Resistance
Glioma
Neoplastic Stem Cells
Apoptosis
ATP-Binding Cassette Transporters
P-Glycoprotein
Camptothecin
Neural Stem Cells
Multiple Drug Resistance
Glioblastoma
Doxorubicin
Neoplasms
Radiotherapy
Stem Cells
Research Personnel
Recurrence
Drug Therapy
Messenger RNA
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Overexpression of CD133 promotes drug resistance in C6 glioma cells. / Angelastro, James M; Lamé, Michael W.

In: Molecular Cancer Research, Vol. 8, No. 8, 08.2010, p. 1105-1115.

Research output: Contribution to journalArticle

@article{085caba8b6084c2780c16e0a12d030cc,
title = "Overexpression of CD133 promotes drug resistance in C6 glioma cells",
abstract = "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.",
author = "Angelastro, {James M} and Lam{\'e}, {Michael W.}",
year = "2010",
month = "8",
doi = "10.1158/1541-7786.MCR-09-0383",
language = "English (US)",
volume = "8",
pages = "1105--1115",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Overexpression of CD133 promotes drug resistance in C6 glioma cells

AU - Angelastro, James M

AU - Lamé, Michael W.

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77955761867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955761867&partnerID=8YFLogxK

U2 - 10.1158/1541-7786.MCR-09-0383

DO - 10.1158/1541-7786.MCR-09-0383

M3 - Article

VL - 8

SP - 1105

EP - 1115

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 8

ER -