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The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans
The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 va...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961974/ https://www.ncbi.nlm.nih.gov/pubmed/36835468 http://dx.doi.org/10.3390/ijms24044060 |
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author | Iden, Jennifer Ana Raphael-Mizrahi, Bitya Awida, Zamzam Naim, Aaron Zyc, Dan Liron, Tamar Kasher, Melody Livshits, Gregory Vered, Marilena Gabet, Yankel |
author_facet | Iden, Jennifer Ana Raphael-Mizrahi, Bitya Awida, Zamzam Naim, Aaron Zyc, Dan Liron, Tamar Kasher, Melody Livshits, Gregory Vered, Marilena Gabet, Yankel |
author_sort | Iden, Jennifer Ana |
collection | PubMed |
description | The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2(−/−)) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (Apc(Min/+)). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2(−/−) mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2(−/−) and Apc(Min/+)CB2(−/−) mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans. Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients. |
format | Online Article Text |
id | pubmed-9961974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99619742023-02-26 The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans Iden, Jennifer Ana Raphael-Mizrahi, Bitya Awida, Zamzam Naim, Aaron Zyc, Dan Liron, Tamar Kasher, Melody Livshits, Gregory Vered, Marilena Gabet, Yankel Int J Mol Sci Article The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2(−/−)) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (Apc(Min/+)). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2(−/−) mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2(−/−) and Apc(Min/+)CB2(−/−) mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans. Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients. MDPI 2023-02-17 /pmc/articles/PMC9961974/ /pubmed/36835468 http://dx.doi.org/10.3390/ijms24044060 Text en © 2023 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 Iden, Jennifer Ana Raphael-Mizrahi, Bitya Awida, Zamzam Naim, Aaron Zyc, Dan Liron, Tamar Kasher, Melody Livshits, Gregory Vered, Marilena Gabet, Yankel The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title | The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title_full | The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title_fullStr | The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title_full_unstemmed | The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title_short | The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans |
title_sort | anti-tumorigenic role of cannabinoid receptor 2 in colon cancer: a study in mice and humans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961974/ https://www.ncbi.nlm.nih.gov/pubmed/36835468 http://dx.doi.org/10.3390/ijms24044060 |
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