Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas

During peritoneal metastasis, cancer cells spread from abdominal solid tumors, disseminate through the peritoneal fluid and attach to and invade through mesothelial cells (MCs) that line the peritoneum. Intestinal adenocarcinomas originating in the mucosa infiltrate the submucosa, muscle layer, and...

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Detalhes bibliográficos
Autores: Gordillo, Carlos H., Sandoval, Pilar, Muñoz-Hernández, Patricia, López-Cabrera, Manuel, Jiménez-Heffernan, José A.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/237440
Acesso em linha:http://hdl.handle.net/10261/237440
Access Level:Acceso aberto
Palavra-chave:Carcinoma-associated fibroblasts
Mesothelial-to-mesenchymal transition
Colorectal cancer
Peritoneal metastasis
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spelling Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomasGordillo, Carlos H.Sandoval, PilarMuñoz-Hernández, PatriciaLópez-Cabrera, ManuelJiménez-Heffernan, José A.Carcinoma-associated fibroblastsMesothelial-to-mesenchymal transitionColorectal cancerPeritoneal metastasisDuring peritoneal metastasis, cancer cells spread from abdominal solid tumors, disseminate through the peritoneal fluid and attach to and invade through mesothelial cells (MCs) that line the peritoneum. Intestinal adenocarcinomas originating in the mucosa infiltrate the submucosa, muscle layer, and serosa in order to finally colonize the peritoneal cavity. However, the mechanism by which metastatic cells leave the primary tumor and reach the peritoneal cavity has not been previously described. Hence, we investigate whether MCs lining visceral peritoneum, through a mesothelial-to-mesenchymal transition (MMT), are a source of carcinoma-associated fibroblasts (CAFs), which could contribute to cancer progression toward the peritoneal cavity. CAFs detected in biopsies from patients with superficially invasive colorectal cancer differed from locally advanced tumors. An aberrant accumulation of myofibroblasts expressing mesothelial markers was found in the stroma of deeply infiltrative tumors located in the neighborhood of a frequently activated mesothelium. We suggest that MMT is a key event in the early stages of peritoneal dissemination.Spanish Ministry of Economy, Industry andCompetitiveness/Fondo Europeo de Desarrollo Regional (MINECO/FEDER) (SAF2016-80648-R)Multidisciplinary Digital Publishing InstituteMinisterio de Economía, Industria y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/237440reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/cancers12020499Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2374402026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
title Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
spellingShingle Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
Gordillo, Carlos H.
Carcinoma-associated fibroblasts
Mesothelial-to-mesenchymal transition
Colorectal cancer
Peritoneal metastasis
title_short Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
title_full Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
title_fullStr Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
title_full_unstemmed Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
title_sort Mesothelial-to-mesenchymal transition contributes to the generation of carcinoma-associated fibroblasts in locally advanced primary colorectal carcinomas
dc.creator.none.fl_str_mv Gordillo, Carlos H.
Sandoval, Pilar
Muñoz-Hernández, Patricia
López-Cabrera, Manuel
Jiménez-Heffernan, José A.
author Gordillo, Carlos H.
author_facet Gordillo, Carlos H.
Sandoval, Pilar
Muñoz-Hernández, Patricia
López-Cabrera, Manuel
Jiménez-Heffernan, José A.
author_role author
author2 Sandoval, Pilar
Muñoz-Hernández, Patricia
López-Cabrera, Manuel
Jiménez-Heffernan, José A.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Carcinoma-associated fibroblasts
Mesothelial-to-mesenchymal transition
Colorectal cancer
Peritoneal metastasis
topic Carcinoma-associated fibroblasts
Mesothelial-to-mesenchymal transition
Colorectal cancer
Peritoneal metastasis
description During peritoneal metastasis, cancer cells spread from abdominal solid tumors, disseminate through the peritoneal fluid and attach to and invade through mesothelial cells (MCs) that line the peritoneum. Intestinal adenocarcinomas originating in the mucosa infiltrate the submucosa, muscle layer, and serosa in order to finally colonize the peritoneal cavity. However, the mechanism by which metastatic cells leave the primary tumor and reach the peritoneal cavity has not been previously described. Hence, we investigate whether MCs lining visceral peritoneum, through a mesothelial-to-mesenchymal transition (MMT), are a source of carcinoma-associated fibroblasts (CAFs), which could contribute to cancer progression toward the peritoneal cavity. CAFs detected in biopsies from patients with superficially invasive colorectal cancer differed from locally advanced tumors. An aberrant accumulation of myofibroblasts expressing mesothelial markers was found in the stroma of deeply infiltrative tumors located in the neighborhood of a frequently activated mesothelium. We suggest that MMT is a key event in the early stages of peritoneal dissemination.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/237440
url http://hdl.handle.net/10261/237440
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/cancers12020499
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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