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Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase
Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs...
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/PMC9867023/ https://www.ncbi.nlm.nih.gov/pubmed/36674635 http://dx.doi.org/10.3390/ijms24021118 |
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author | Okamoto, Michio Mizuno, Rei Kawada, Kenji Itatani, Yoshiro Kiyasu, Yoshiyuki Hanada, Keita Hirata, Wataru Nishikawa, Yasuyo Masui, Hideyuki Sugimoto, Naoko Tamura, Takuya Inamoto, Susumu Sakai, Yoshiharu Obama, Kazutaka |
author_facet | Okamoto, Michio Mizuno, Rei Kawada, Kenji Itatani, Yoshiro Kiyasu, Yoshiyuki Hanada, Keita Hirata, Wataru Nishikawa, Yasuyo Masui, Hideyuki Sugimoto, Naoko Tamura, Takuya Inamoto, Susumu Sakai, Yoshiharu Obama, Kazutaka |
author_sort | Okamoto, Michio |
collection | PubMed |
description | Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases. |
format | Online Article Text |
id | pubmed-9867023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98670232023-01-22 Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase Okamoto, Michio Mizuno, Rei Kawada, Kenji Itatani, Yoshiro Kiyasu, Yoshiyuki Hanada, Keita Hirata, Wataru Nishikawa, Yasuyo Masui, Hideyuki Sugimoto, Naoko Tamura, Takuya Inamoto, Susumu Sakai, Yoshiharu Obama, Kazutaka Int J Mol Sci Article Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases. MDPI 2023-01-06 /pmc/articles/PMC9867023/ /pubmed/36674635 http://dx.doi.org/10.3390/ijms24021118 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 Okamoto, Michio Mizuno, Rei Kawada, Kenji Itatani, Yoshiro Kiyasu, Yoshiyuki Hanada, Keita Hirata, Wataru Nishikawa, Yasuyo Masui, Hideyuki Sugimoto, Naoko Tamura, Takuya Inamoto, Susumu Sakai, Yoshiharu Obama, Kazutaka Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title | Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title_full | Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title_fullStr | Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title_full_unstemmed | Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title_short | Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase |
title_sort | neutrophil extracellular traps promote metastases of colorectal cancers through activation of erk signaling by releasing neutrophil elastase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867023/ https://www.ncbi.nlm.nih.gov/pubmed/36674635 http://dx.doi.org/10.3390/ijms24021118 |
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