Cargando…

The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer

Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). Previous studies have shown that TAMs play a dual role in the development of colorectal cancer and promote the additional exploration of the immune escape of colorectal cancer. Studies have confirmed...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiang, Manman, Cui, Hongquan, Liu, Zhihong, Zhou, Xin, Zhang, Ling, Cao, Longnv, Wang, Miao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776905/
https://www.ncbi.nlm.nih.gov/pubmed/36552870
http://dx.doi.org/10.3390/cells11244106
_version_ 1784855973578407936
author Jiang, Manman
Cui, Hongquan
Liu, Zhihong
Zhou, Xin
Zhang, Ling
Cao, Longnv
Wang, Miao
author_facet Jiang, Manman
Cui, Hongquan
Liu, Zhihong
Zhou, Xin
Zhang, Ling
Cao, Longnv
Wang, Miao
author_sort Jiang, Manman
collection PubMed
description Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). Previous studies have shown that TAMs play a dual role in the development of colorectal cancer and promote the additional exploration of the immune escape of colorectal cancer. Studies have confirmed that macrophages utilize amino acid metabolism under the stimulation of some factors released by tumor cells, thus affecting the direction of polarization. Therefore, we investigated the effect of amino acid metabolism on macrophage function and the involved mechanism. Based on the comprehensive analysis of the GSE18804 GEO dataset and amino acid metabolism pathway, we identified the eight key enzymes of amino acid metabolism in colon TAMs, namely, ACADM, ACADS, GPX4, GSR, HADH, HMGCL, HMGCS1 and IDH1. We then evaluated the expression, survival analysis and relationship of clinicopathological features with these eight key enzymes. The results supported the critical role of these eight genes in colorectal cancer. Macrophages phagocytose tumor cells, and these eight key enzymes were identified in combination with GPX4, a critical protein of ferroptosis, suggesting that the change in the expression of these eight key enzymes in TAMs may be involved in the regulation of colorectal cancer through cell death. Correlation analysis of three programmed cell death (PCD) marker genes indicated that these eight key enzymes may cause macrophage death through pyroptosis, leading to immune escape of colorectal cancer. We also investigated the regulation of ACADS in CRC using flow cytometry, qPCR and ELISAs, which demonstrated that an ACADS deficiency polarizes TAMs to M2 macrophages. In summary, the present study revealed the relationship between amino acid metabolism and the cell death of macrophages, providing a new research direction for the molecular mechanism of macrophage polarization.
format Online
Article
Text
id pubmed-9776905
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97769052022-12-23 The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer Jiang, Manman Cui, Hongquan Liu, Zhihong Zhou, Xin Zhang, Ling Cao, Longnv Wang, Miao Cells Article Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). Previous studies have shown that TAMs play a dual role in the development of colorectal cancer and promote the additional exploration of the immune escape of colorectal cancer. Studies have confirmed that macrophages utilize amino acid metabolism under the stimulation of some factors released by tumor cells, thus affecting the direction of polarization. Therefore, we investigated the effect of amino acid metabolism on macrophage function and the involved mechanism. Based on the comprehensive analysis of the GSE18804 GEO dataset and amino acid metabolism pathway, we identified the eight key enzymes of amino acid metabolism in colon TAMs, namely, ACADM, ACADS, GPX4, GSR, HADH, HMGCL, HMGCS1 and IDH1. We then evaluated the expression, survival analysis and relationship of clinicopathological features with these eight key enzymes. The results supported the critical role of these eight genes in colorectal cancer. Macrophages phagocytose tumor cells, and these eight key enzymes were identified in combination with GPX4, a critical protein of ferroptosis, suggesting that the change in the expression of these eight key enzymes in TAMs may be involved in the regulation of colorectal cancer through cell death. Correlation analysis of three programmed cell death (PCD) marker genes indicated that these eight key enzymes may cause macrophage death through pyroptosis, leading to immune escape of colorectal cancer. We also investigated the regulation of ACADS in CRC using flow cytometry, qPCR and ELISAs, which demonstrated that an ACADS deficiency polarizes TAMs to M2 macrophages. In summary, the present study revealed the relationship between amino acid metabolism and the cell death of macrophages, providing a new research direction for the molecular mechanism of macrophage polarization. MDPI 2022-12-17 /pmc/articles/PMC9776905/ /pubmed/36552870 http://dx.doi.org/10.3390/cells11244106 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiang, Manman
Cui, Hongquan
Liu, Zhihong
Zhou, Xin
Zhang, Ling
Cao, Longnv
Wang, Miao
The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title_full The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title_fullStr The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title_full_unstemmed The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title_short The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer
title_sort role of amino acid metabolism of tumor associated macrophages in the development of colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776905/
https://www.ncbi.nlm.nih.gov/pubmed/36552870
http://dx.doi.org/10.3390/cells11244106
work_keys_str_mv AT jiangmanman theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT cuihongquan theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT liuzhihong theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT zhouxin theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT zhangling theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT caolongnv theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT wangmiao theroleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT jiangmanman roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT cuihongquan roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT liuzhihong roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT zhouxin roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT zhangling roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT caolongnv roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer
AT wangmiao roleofaminoacidmetabolismoftumorassociatedmacrophagesinthedevelopmentofcolorectalcancer