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Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids.
MedLine Citation:
PMID:  21907927     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The development of resistance to chemotherapy is a major obstacle for lasting effective treatment of cancer. Here, we demonstrate that endogenous mesenchymal stem cells (MSCs) become activated during treatment with platinum analogs and secrete factors that protect tumor cells against a range of chemotherapeutics. Through a metabolomics approach, we identified two distinct platinum-induced polyunsaturated fatty acids (PIFAs), 12-oxo-5,8,10-heptadecatrienoic acid (KHT) and hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3)), that in minute quantities induce resistance to a broad spectrum of chemotherapeutic agents. Interestingly, blocking central enzymes involved in the production of these PIFAs (cyclooxygenase-1 and thromboxane synthase) prevents MSC-induced resistance. Our findings show that MSCs are potent mediators of resistance to chemotherapy and reveal targets to enhance chemotherapy efficacy in patients.
Authors:
Jeanine M L Roodhart; Laura G M Daenen; Edwin C A Stigter; Henk-Jan Prins; Johan Gerrits; Julia M Houthuijzen; Marije G Gerritsen; Henk S Schipper; Marieke J G Backer; Miranda van Amersfoort; Joost S P Vermaat; Petra Moerer; Kenji Ishihara; Eric Kalkhoven; Jos H Beijnen; Patrick W B Derksen; Rene H Medema; Anton C Martens; Arjan B Brenkman; Emile E Voest
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer cell     Volume:  20     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  370-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Medical Oncology (F02.126), University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
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