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Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer

Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma p...

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Autores principales: Makutani, Yusuke, Kawakami, Hisato, Tsujikawa, Takahiro, Yoshimura, Kanako, Chiba, Yasutaka, Ito, Akihiko, Kawamura, Junichiro, Haratani, Koji, Nakagawa, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424903/
https://www.ncbi.nlm.nih.gov/pubmed/36052235
http://dx.doi.org/10.3389/fonc.2022.956270
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author Makutani, Yusuke
Kawakami, Hisato
Tsujikawa, Takahiro
Yoshimura, Kanako
Chiba, Yasutaka
Ito, Akihiko
Kawamura, Junichiro
Haratani, Koji
Nakagawa, Kazuhiko
author_facet Makutani, Yusuke
Kawakami, Hisato
Tsujikawa, Takahiro
Yoshimura, Kanako
Chiba, Yasutaka
Ito, Akihiko
Kawamura, Junichiro
Haratani, Koji
Nakagawa, Kazuhiko
author_sort Makutani, Yusuke
collection PubMed
description Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma patients (n = 592) in The Cancer Genome Atlas. The role of MMP14 in the TME was investigated in a retrospective analysis of tumor samples from 86 individuals with stage III colorectal cancer by single cell–based spatial profiling of MMP14 expression as performed by 12-color multiplex immunohistochemistry (mIHC). Analysis of gene expression data revealed that high MMP14 expression was associated with tumor progression and implicated both cancer-associated fibroblasts (CAFs) and tumor-associated macrophages in such progression. Spatial profiling by mIHC revealed that a higher percentage of MMP14(+) cells among intratumoral CAFs (MMP14(+) CAF/CAF ratio) was associated with poorer relapse-free survival. Multivariable analysis including key clinical factors identified the MMP14(+) CAF/CAF ratio as an independent poor prognostic factor. Moreover, the patient subset with both a high MMP14(+) CAF/CAF ratio and a low tumor-infiltrating lymphocyte density showed the worst prognosis. Our results suggest that MMP14(+) CAFs play an important role in progression of stage III colorectal cancer and may therefore be a promising therapeutic target.
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spelling pubmed-94249032022-08-31 Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer Makutani, Yusuke Kawakami, Hisato Tsujikawa, Takahiro Yoshimura, Kanako Chiba, Yasutaka Ito, Akihiko Kawamura, Junichiro Haratani, Koji Nakagawa, Kazuhiko Front Oncol Oncology Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma patients (n = 592) in The Cancer Genome Atlas. The role of MMP14 in the TME was investigated in a retrospective analysis of tumor samples from 86 individuals with stage III colorectal cancer by single cell–based spatial profiling of MMP14 expression as performed by 12-color multiplex immunohistochemistry (mIHC). Analysis of gene expression data revealed that high MMP14 expression was associated with tumor progression and implicated both cancer-associated fibroblasts (CAFs) and tumor-associated macrophages in such progression. Spatial profiling by mIHC revealed that a higher percentage of MMP14(+) cells among intratumoral CAFs (MMP14(+) CAF/CAF ratio) was associated with poorer relapse-free survival. Multivariable analysis including key clinical factors identified the MMP14(+) CAF/CAF ratio as an independent poor prognostic factor. Moreover, the patient subset with both a high MMP14(+) CAF/CAF ratio and a low tumor-infiltrating lymphocyte density showed the worst prognosis. Our results suggest that MMP14(+) CAFs play an important role in progression of stage III colorectal cancer and may therefore be a promising therapeutic target. Frontiers Media S.A. 2022-08-16 /pmc/articles/PMC9424903/ /pubmed/36052235 http://dx.doi.org/10.3389/fonc.2022.956270 Text en Copyright © 2022 Makutani, Kawakami, Tsujikawa, Yoshimura, Chiba, Ito, Kawamura, Haratani and Nakagawa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Makutani, Yusuke
Kawakami, Hisato
Tsujikawa, Takahiro
Yoshimura, Kanako
Chiba, Yasutaka
Ito, Akihiko
Kawamura, Junichiro
Haratani, Koji
Nakagawa, Kazuhiko
Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title_full Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title_fullStr Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title_full_unstemmed Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title_short Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
title_sort contribution of mmp14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424903/
https://www.ncbi.nlm.nih.gov/pubmed/36052235
http://dx.doi.org/10.3389/fonc.2022.956270
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