Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

Autor: Houthuijzen, Julia M., Oosterom, Ilse, Hudson, Brian D., Hirasawa, Akira, Daenen, Laura G.M., McLean, Chelsea M., Hansen, Steffen V.F., Jaarsveld, Marijn T.M., Peeper, Daniel S., Sadatmand, Sahar Jafari, Roodhart, Jeanine M.L., van de Lest, Chris H.A., Ulven, Trond, Ishihara, Kenji, Milligan, Graeme, Voest, Emile E.
Přispěvatelé: LS Veterinaire biochemie, dB&C FR-RMSC FR, dES RMSC
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: The FASEB Journal
Houthuijzen, J M, Oosterom, I, Hudson, B D, Hirasawa, A, Daenen, L G M, McLean, C M, Hansen, S V F, van Jaarsveld, M T M, Peeper, D S, Jafari Sadatmand, S, Roodhart, J M L, van de Lest, C H A, Ulven, T, Ishihara, K, Milligan, G & Voest, E 2017, ' Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance ', F A S E B Journal, vol. 31, no. 5, pp. 2195-2209 . https://doi.org/10.1096/fj.201601248R
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201601248R
Popis: Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80(+)/CD11b(low) macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80(+)/CD11b(low) macrophages as the relevant receptor for 16:4(n-3). Studies that used splenocytes from GPR120-deficient mice have confirmed this conclusion. Activation of the 16:4(n-3)-GPR120 axis led to enhanced cPLA2 activity in these splenic macrophages and secretion of the resistance-inducing lipid mediator, lysophosphatidylcholine(24:1). These studies identify a novel and unexpected function for GPR120 and suggest that antagonists of this receptor might be effective agents to limit development of chemotherapy resistance.-Houthuijzen, J. M., Oosterom, I., Hudson, B. D., Hirasawa, A., Daenen, L. G. M., McLean, C. M., Hansen, S. V. F., van Jaarsveld, M. T. M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance.
Databáze: OpenAIRE
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