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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0283822 |
| _version_ | 1797843028085309440 |
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| author | Takeshi Takasago Ryohei Hayashi Yoshitaka Ueno Misa Ariyoshi Kana Onishi Ken Yamashita Yuichi Hiyama Hidehiko Takigawa Ryo Yuge Yuji Urabe Shiro Oka Yasuhiko Kitadai Shinji Tanaka |
| author_facet | Takeshi Takasago Ryohei Hayashi Yoshitaka Ueno Misa Ariyoshi Kana Onishi Ken Yamashita Yuichi Hiyama Hidehiko Takigawa Ryo Yuge Yuji Urabe Shiro Oka Yasuhiko Kitadai Shinji Tanaka |
| author_sort | Takeshi Takasago |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T16:57:49Z |
| format | Article |
| id | doaj.art-2742e2ee34aa432899a53f0f9b4892f6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T16:57:49Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2742e2ee34aa432899a53f0f9b4892f62023-04-21T05:34:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183e028382210.1371/journal.pone.0283822Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model.Takeshi TakasagoRyohei HayashiYoshitaka UenoMisa AriyoshiKana OnishiKen YamashitaYuichi HiyamaHidehiko TakigawaRyo YugeYuji UrabeShiro OkaYasuhiko KitadaiShinji TanakaThe 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.https://doi.org/10.1371/journal.pone.0283822 |
| spellingShingle | Takeshi Takasago Ryohei Hayashi Yoshitaka Ueno Misa Ariyoshi Kana Onishi Ken Yamashita Yuichi Hiyama Hidehiko Takigawa Ryo Yuge Yuji Urabe Shiro Oka Yasuhiko Kitadai Shinji Tanaka Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0283822 |
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