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Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics
BACKGROUND: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500191/ https://www.ncbi.nlm.nih.gov/pubmed/32943450 http://dx.doi.org/10.1136/jitc-2020-000638 |
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author | Rabold, Katrin Aschenbrenner, Anna Thiele, Christoph Boahen, Collins K Schiltmans, Alexander Smit, Johannes W A Schultze, Joachim L Netea, Mihai G Adema, Gosse J Netea-Maier, Romana T |
author_facet | Rabold, Katrin Aschenbrenner, Anna Thiele, Christoph Boahen, Collins K Schiltmans, Alexander Smit, Johannes W A Schultze, Joachim L Netea, Mihai G Adema, Gosse J Netea-Maier, Romana T |
author_sort | Rabold, Katrin |
collection | PubMed |
description | BACKGROUND: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs. METHODS: In a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways. RESULTS: Based on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME. CONCLUSIONS: Taken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME. |
format | Online Article Text |
id | pubmed-7500191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-75001912020-10-05 Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics Rabold, Katrin Aschenbrenner, Anna Thiele, Christoph Boahen, Collins K Schiltmans, Alexander Smit, Johannes W A Schultze, Joachim L Netea, Mihai G Adema, Gosse J Netea-Maier, Romana T J Immunother Cancer Basic Tumor Immunology BACKGROUND: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs. METHODS: In a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways. RESULTS: Based on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME. CONCLUSIONS: Taken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME. BMJ Publishing Group 2020-09-17 /pmc/articles/PMC7500191/ /pubmed/32943450 http://dx.doi.org/10.1136/jitc-2020-000638 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Basic Tumor Immunology Rabold, Katrin Aschenbrenner, Anna Thiele, Christoph Boahen, Collins K Schiltmans, Alexander Smit, Johannes W A Schultze, Joachim L Netea, Mihai G Adema, Gosse J Netea-Maier, Romana T Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title | Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title_full | Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title_fullStr | Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title_full_unstemmed | Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title_short | Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
title_sort | enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics |
topic | Basic Tumor Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500191/ https://www.ncbi.nlm.nih.gov/pubmed/32943450 http://dx.doi.org/10.1136/jitc-2020-000638 |
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