Title of article
Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids
Author/Authors
Erik and Roodhart، نويسنده , , Jeanine M.L. and Daenen، نويسنده , , Laura G.M. and Stigter، نويسنده , , Edwin C.A. and Prins، نويسنده , , Henk-Jan and Gerrits، نويسنده , , Johan and Houthuijzen، نويسنده , , Julia M. and Gerritsen، نويسنده , , Marije G. and Schipper، نويسنده , , Henk S. and Backer، نويسنده , , Marieke J.G. and van Amersfoort، نويسنده , , Miranda and Vermaat، نويسنده , , Joost S.P. and Moerer، نويسنده , , Petra and Ishihara، نويسنده , , Kenji and Kalkhoven، نويسنده , , Eric and Beijnen، نويسنده , , Jos H. and Derksen، نويسنده , , Patrick W.B. and Medema، نويسنده , , Rene H. and Martens، نويسنده , , Anton C. and Brenkman، نويسنده , , Arjan B. and Voest، نويسنده , , Emile E.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2011
Pages
14
From page
370
To page
383
Abstract
Summary
velopment 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.
Journal title
Cancer Cell
Serial Year
2011
Journal title
Cancer Cell
Record number
1337629
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