This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objectives: New data suggest that glioma stem-like cells (GSCs) and neural stem/progenitor cells (NSCs) may share common origins. GSCs drive tumor proliferation and appear to be resistant to classic chemotherapy, while the effects of chemotherapy on NSCs are not well studied. As the role of NSCs in learning and memory is increasingly recognized, we need to identify drugs that reduce neurotoxicity but are still effective against glial tumors.
Methods: We treated 3 human NSC cultures and multiple low- and high-grade GSC cultures with the commonly used agents temozolomide (TMZ) and cisplatin (CIS), and with 2 newer, promising drugs: the proteasome inhibitor bortezomib (BTZ) and the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (ERL). We measured cell survival, proliferation, cell death induction, and drug resistance markers.
Results: TMZ decreased NSC viability, while minimally affecting GSCs. TMZ induced NSC death, which was partially compensated for by increased proliferation. CIS had similar effects. The NSC's sensitivity to TMZ and CIS correlated with low expression of the multidrug resistance gene ABCG2, but not of MGMT or MSH1/MLH2. BTZ caused an 80%decrease in GSCs, while minimally affecting NSCs. GSCs had lower proteasome levels and activity after BTZ treatment. ERL treatment also decreased GSC numbers, but not NSC viability, which correlated with low EGFR expression in NSCs compared to GSCs.
Conclusions: Newer chemotherapy agents ERL and BTZ are effective against GSCs yet produce minimal effects on NSCs, while the older drugs TMZ and CIS are more toxic for NSCs than for GSCs. The identification and testing of more selective drugs is clearly warranted.
Footnotes
Study funding: Supported in part by start-up funds to D. Bota from the University of California, Irvine, and by Children's Hospital of Orange County through the National Human Neural Stem Cell Resource.
-
- BTZ
- bortezomib
- CIS
- cisplatin
- ERL
- erlotinib
- GSC
- glioma stem-like cell
- MGMT
- methyl-guanine methyl transferase
- NSC
- neural stem/progenitor cell
- TMZ
- temozolomide
-
Editorial, page 1118
-
Supplemental data at www.neurology.org
- Received May 20, 2010.
- Accepted October 15, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
AAN Members: Sign in with your AAN member credentials (e-mail or 6-digit Member ID number)
Non-AAN Member subscribers: Sign in with subscriber credentials
Log in using your username and password
Purchase access
Disputes & Debates: Rapid online correspondence
- Neural stem/progenitors and glioma stem-like cells have differential sensitivity to chemotherapy
- Reply from the Authors
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within the last 8 weeks.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.