Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids.
Cancer Cell
; 20(3): 370-83, 2011 Sep 13.
Article
en En
| MEDLINE
| ID: mdl-21907927
ABSTRACT
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 (164(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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tromboxano-A Sintasa
/
Compuestos de Platino
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Resistencia a Antineoplásicos
/
Ciclooxigenasa 1
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Ácidos Grasos
/
Ácidos Grasos Insaturados
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Células Madre Mesenquimatosas
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Países Bajos