Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge
Abstract Background The incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3315 |
| _version_ | 1818254243342057472 |
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| author | Katharina M. Scheurlen Adrian T. Billeter Stephen J. O'Brien Susan Galandiuk |
| author_facet | Katharina M. Scheurlen Adrian T. Billeter Stephen J. O'Brien Susan Galandiuk |
| author_sort | Katharina M. Scheurlen |
| collection | DOAJ |
| description | Abstract Background The incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an association between metabolic dysfunction and carcinogenesis. Tumor‐associated macrophages (TAMs) are able to orchestrate tumor promoting and suppressing mechanisms in CRC. The aim of this review was to discuss the different roles of TAMs in CRC and their phenotype‐specific metabolic pathways to identify potential new targets for CRC treatment. Methods A literature search was performed using PubMed, Cochrane and Embase to identify studies on TAMs and their metabolism in CRC. The following search terms were used in various combinations: (obesity OR adiposity OR obese) AND (macrophage OR polarization OR macrophage metabolism) AND ((colon cancer*) OR (colon carcinoma) OR (colonic tumor*) OR (colonic neoplasm[MeSH]) OR (rectal cancer*) OR (rectal carcinoma) OR (rectal tumor*) OR (rectal neoplasm[MeSH]) OR (colorectal cancer*) OR (colorectal carcinoma) OR (colorectal tumor*) OR (colorectal neoplasm[MeSH])). Studies including data on the phenotype and metabolism of TAMs in CRC were analyzed. Results Evidence for the prognostic utility of macrophage markers in CRC is currently evolving, with a particular role of stage‐dependent cellular metabolism profiles of TAMs. Itaconate is one of the metabolites produced by proinflammatory subtypes of TAMs and it is known to have tumor promoting effects. Metabolic pathways that are involved in macrophage activation and reprogramming play a role in a chronic inflammatory setting, consequently affecting the onset and development of CRC. Conclusions Tumor‐promoting metabolites, such as itaconate, are directly regulating these mechanisms, thereby triggering carcinogenesis. Metabolic reprogramming in TAMs can build a bridge between metabolic dysfunction and the onset and progression of CRC through inflammatory pathways, particularly in younger patients with early‐onset CRC. |
| first_indexed | 2024-12-12T16:52:52Z |
| format | Article |
| id | doaj.art-8138246a6a8e4f5692e343c3faf94c8d |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-12T16:52:52Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8138246a6a8e4f5692e343c3faf94c8d2022-12-22T00:18:20ZengWileyCancer Medicine2045-76342020-09-019186679669310.1002/cam4.3315Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridgeKatharina M. Scheurlen0Adrian T. Billeter1Stephen J. O'Brien2Susan Galandiuk3Price Institute of Surgical Research Department of Surgery University of Louisville Louisville KY USADepartment of General, Visceral, and Transplantation Surgery University Hospital Heidelberg Heidelberg Baden‐Wuerttemberg GermanyPrice Institute of Surgical Research Department of Surgery University of Louisville Louisville KY USAPrice Institute of Surgical Research Department of Surgery University of Louisville Louisville KY USAAbstract Background The incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an association between metabolic dysfunction and carcinogenesis. Tumor‐associated macrophages (TAMs) are able to orchestrate tumor promoting and suppressing mechanisms in CRC. The aim of this review was to discuss the different roles of TAMs in CRC and their phenotype‐specific metabolic pathways to identify potential new targets for CRC treatment. Methods A literature search was performed using PubMed, Cochrane and Embase to identify studies on TAMs and their metabolism in CRC. The following search terms were used in various combinations: (obesity OR adiposity OR obese) AND (macrophage OR polarization OR macrophage metabolism) AND ((colon cancer*) OR (colon carcinoma) OR (colonic tumor*) OR (colonic neoplasm[MeSH]) OR (rectal cancer*) OR (rectal carcinoma) OR (rectal tumor*) OR (rectal neoplasm[MeSH]) OR (colorectal cancer*) OR (colorectal carcinoma) OR (colorectal tumor*) OR (colorectal neoplasm[MeSH])). Studies including data on the phenotype and metabolism of TAMs in CRC were analyzed. Results Evidence for the prognostic utility of macrophage markers in CRC is currently evolving, with a particular role of stage‐dependent cellular metabolism profiles of TAMs. Itaconate is one of the metabolites produced by proinflammatory subtypes of TAMs and it is known to have tumor promoting effects. Metabolic pathways that are involved in macrophage activation and reprogramming play a role in a chronic inflammatory setting, consequently affecting the onset and development of CRC. Conclusions Tumor‐promoting metabolites, such as itaconate, are directly regulating these mechanisms, thereby triggering carcinogenesis. Metabolic reprogramming in TAMs can build a bridge between metabolic dysfunction and the onset and progression of CRC through inflammatory pathways, particularly in younger patients with early‐onset CRC.https://doi.org/10.1002/cam4.3315adipositycolonic neoplasmscolorectal neoplasmsobesityrectal neoplasmstumor‐associated macrophages |
| spellingShingle | Katharina M. Scheurlen Adrian T. Billeter Stephen J. O'Brien Susan Galandiuk Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge Cancer Medicine adiposity colonic neoplasms colorectal neoplasms obesity rectal neoplasms tumor‐associated macrophages |
| title | Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge |
| title_full | Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge |
| title_fullStr | Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge |
| title_full_unstemmed | Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge |
| title_short | Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge |
| title_sort | metabolic dysfunction and early onset colorectal cancer how macrophages build the bridge |
| topic | adiposity colonic neoplasms colorectal neoplasms obesity rectal neoplasms tumor‐associated macrophages |
| url | https://doi.org/10.1002/cam4.3315 |
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