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Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model

The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor sup...

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Autores principales: Takasago, Takeshi, Hayashi, Ryohei, Ueno, Yoshitaka, Ariyoshi, Misa, Onishi, Kana, Yamashita, Ken, Hiyama, Yuichi, Takigawa, Hidehiko, Yuge, Ryo, Urabe, Yuji, Oka, Shiro, Kitadai, Yasuhiko, Tanaka, Shinji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062630/
https://www.ncbi.nlm.nih.gov/pubmed/36996146
http://dx.doi.org/10.1371/journal.pone.0283822
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author Takasago, Takeshi
Hayashi, Ryohei
Ueno, Yoshitaka
Ariyoshi, Misa
Onishi, Kana
Yamashita, Ken
Hiyama, Yuichi
Takigawa, Hidehiko
Yuge, Ryo
Urabe, Yuji
Oka, Shiro
Kitadai, Yasuhiko
Tanaka, Shinji
author_facet Takasago, Takeshi
Hayashi, Ryohei
Ueno, Yoshitaka
Ariyoshi, Misa
Onishi, Kana
Yamashita, Ken
Hiyama, Yuichi
Takigawa, Hidehiko
Yuge, Ryo
Urabe, Yuji
Oka, Shiro
Kitadai, Yasuhiko
Tanaka, Shinji
author_sort Takasago, Takeshi
collection PubMed
description The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model.
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spelling pubmed-100626302023-03-31 Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model Takasago, Takeshi Hayashi, Ryohei Ueno, Yoshitaka Ariyoshi, Misa Onishi, Kana Yamashita, Ken Hiyama, Yuichi Takigawa, Hidehiko Yuge, Ryo Urabe, Yuji Oka, Shiro Kitadai, Yasuhiko Tanaka, Shinji PLoS One Research Article The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model. Public Library of Science 2023-03-30 /pmc/articles/PMC10062630/ /pubmed/36996146 http://dx.doi.org/10.1371/journal.pone.0283822 Text en © 2023 Takasago et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Takasago, Takeshi
Hayashi, Ryohei
Ueno, Yoshitaka
Ariyoshi, Misa
Onishi, Kana
Yamashita, Ken
Hiyama, Yuichi
Takigawa, Hidehiko
Yuge, Ryo
Urabe, Yuji
Oka, Shiro
Kitadai, Yasuhiko
Tanaka, Shinji
Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title_full Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title_fullStr Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title_full_unstemmed Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title_short Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
title_sort anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062630/
https://www.ncbi.nlm.nih.gov/pubmed/36996146
http://dx.doi.org/10.1371/journal.pone.0283822
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