Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids, 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#, and Emile E. Voest#
# Equal contribution
Published in Cancer Cell 20, 370–383, September 13, 2011
Chemoresistance is one of the most prominent problems that cancer patients face, particularly when the cancer has disseminated, causing high morbidity and mortality.
By using a metabolomics approach, involving state-of-the-art sample preprocessing, liquid chromatography, metabolite identification and mass spectrometry, Dr. Arjan Brenkman who heads the biology-driven metabolomics research program in the UMC Utrecht identified and characterized two specific lipids that prevent the action of a broad range of chemotherapy agents in cancer treatment in the study which was co-led by UMC Utrecht clinical oncologist Prof. Dr. Emile Voest.
Remarkably, these lipids are produced by our own stem cells, which is a novel concept in the chemotherapy resistance field. Moreover, we have identified the pathway by which these lipids are produced and identified existing drugs to block this.
Surprisingly, these fats are also highly present in some off-the-shelf fish oils. Indeed, oral intake of these fish oils leads to massive chemoresistance in our cancer models and based on these experiments, Prof. Dr. Emile Voest, now advises not to use fish oils during chemotherapy pending further studies.