Modulation of the colon cancer cell phenotype by pro-inflammatory macrophages: A preclinical model of surgery-associated inflammation and tumor recurrence
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- dc.contributor.author Marcuello, María
- dc.contributor.author Mayol Girbau, Xavier
- dc.contributor.author Felipe-Fumero, Eloísa
- dc.contributor.author Costa, Jaume
- dc.contributor.author López-Hierro, Laia
- dc.contributor.author Salvans Ruiz, Silvia
- dc.contributor.author Alonso Gonçalves, Sandra
- dc.contributor.author Pascual Damieta, Marta
- dc.contributor.author Grande Posa, Luís
- dc.contributor.author Pera Roman, Miguel
- dc.date.accessioned 2019-01-15T08:04:46Z
- dc.date.available 2019-01-15T08:04:46Z
- dc.date.issued 2018
- dc.description.abstract Peritoneal infection after colorectal cancer surgery is associated with a higher rate of tumor relapse. We have recently proposed that soluble inflammatory factors released in response to a postoperative infection enhance tumor progression features in residual tumor cells. In an effort to set up models to study the mechanisms of residual tumor cell activation during surgery-associated inflammation, we have analyzed the phenotypic response of colon cancer cell lines to the paracrine effects of THP-1 and U937 differentiated human macrophages, which release an inflammatory medium characteristic of an innate immune response. The exposure of the colon cancer cell lines HT-29 and SW620 to conditioned media isolated from differentiated THP-1 and U937 macrophages induced a mesenchymal-like phenotypic shift, involving the activation of in vitro invasiveness. The inflammatory media activated the β-catenin/TCF4 transcriptional pathway and induced the expression of several mesenchymal (e.g., FN1 and VIM) and TCF4 target genes (e.g., MMP7, PTGS2, MET, and CCD1). Similarly, differential expression of some transcription factors involved in epithelial-to-mesenchymal transitions (i.e. ZEB1, SNAI1, and SNAI2) was variably observed in the colon cancer cell lines when exposed to the inflammatory media. THP-1 and U937 macrophages, which displayed characteristics of M1 differentiation, overexpressed some cytokines previously shown to be induced in colorectal cancer patients with increased rates of tumor recurrence associated with postoperative peritoneal infections, thus suggesting their pro-tumoral character. Therefore, the environment created by inflammatory M1 macrophages enhances features of epithelial-to-mesenchymal transition, and may be useful as a model to characterize pro-inflammatory cytokines as putative biomarkers of tumor recurrence risk.
- dc.format.mimetype application/pdf
- dc.identifier.citation Marcuello M, Mayol X, Felipe-Fumero E, Costa J, López-Hierro L, Salvans S. et al. Modulation of the colon cancer cell phenotype by pro-inflammatory macrophages: A preclinical model of surgery-associated inflammation and tumor recurrence. PLoS One. 2018 Feb 20;13(2):e0192958. DOI: 10.1371/journal.pone.0192958
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0192958
- dc.identifier.issn 1932-6203
- dc.identifier.uri http://hdl.handle.net/10230/36266
- dc.language.iso eng
- dc.publisher Public Library of Science (PLoS)
- dc.relation.ispartof PLoS One. 2018 Feb 20;13(2):e0192958
- dc.rights Copyright © 2018 Marcuello et al. 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.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.other Còlon -- Càncer -- Aspectes genètics
- dc.title Modulation of the colon cancer cell phenotype by pro-inflammatory macrophages: A preclinical model of surgery-associated inflammation and tumor recurrence
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion