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Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment in non-medullary thyroid cancer (TC), the most common endocrine malignancy. However, little is known regarding the regulation of their function in TC. Transcriptome analysis in a model of TC-induced macrophages iden...

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Detalles Bibliográficos
Autores principales: Arts, Rob J. W., Plantinga, Theo S., Tuit, Sander, Ulas, Thomas, Heinhuis, Bas, Tesselaar, Marika, Sloot, Yvette, Adema, Gosse J., Joosten, Leo A. B., Smit, Johannes W. A., Netea, Mihai G., Schultze, Joachim L., Netea-Maier, Romana T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5213309/
https://www.ncbi.nlm.nih.gov/pubmed/28123869
http://dx.doi.org/10.1080/2162402X.2016.1229725
Descripción
Sumario:Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment in non-medullary thyroid cancer (TC), the most common endocrine malignancy. However, little is known regarding the regulation of their function in TC. Transcriptome analysis in a model of TC-induced macrophages identified increased inflammatory characteristics and rewiring of cell metabolism as key functional changes. This functional reprogramming was partly mediated by TC-derived lactate that induced upregulation of cytokine production through an AKT1/mTOR-dependent increase in aerobic glycolysis. This led to epigenetic modifications at the level of histone methylation, and subsequently long-term functional changes. Immunohistochemistry assessment validated the increase in glycolysis enzymes and lactate receptor in TAMs in tissue samples from patients with TC. In conclusion, Akt/mTOR-dependent glycolysis mediates TC-induced reprogramming of TAMs and inflammation, and this may represent a novel therapeutic target in TC.