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The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes

Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing thi...

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Autores principales: Fuhr, Luise, Abreu, Mónica, Carbone, Annalucia, El-Athman, Rukeia, Bianchi, Fabrizio, Laukkanen, Mikko O., Mazzoccoli, Gianluigi, Relógio, Angela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678177/
https://www.ncbi.nlm.nih.gov/pubmed/31311174
http://dx.doi.org/10.3390/cancers11070988
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author Fuhr, Luise
Abreu, Mónica
Carbone, Annalucia
El-Athman, Rukeia
Bianchi, Fabrizio
Laukkanen, Mikko O.
Mazzoccoli, Gianluigi
Relógio, Angela
author_facet Fuhr, Luise
Abreu, Mónica
Carbone, Annalucia
El-Athman, Rukeia
Bianchi, Fabrizio
Laukkanen, Mikko O.
Mazzoccoli, Gianluigi
Relógio, Angela
author_sort Fuhr, Luise
collection PubMed
description Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.
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spelling pubmed-66781772019-08-19 The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes Fuhr, Luise Abreu, Mónica Carbone, Annalucia El-Athman, Rukeia Bianchi, Fabrizio Laukkanen, Mikko O. Mazzoccoli, Gianluigi Relógio, Angela Cancers (Basel) Article Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics. MDPI 2019-07-15 /pmc/articles/PMC6678177/ /pubmed/31311174 http://dx.doi.org/10.3390/cancers11070988 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fuhr, Luise
Abreu, Mónica
Carbone, Annalucia
El-Athman, Rukeia
Bianchi, Fabrizio
Laukkanen, Mikko O.
Mazzoccoli, Gianluigi
Relógio, Angela
The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title_full The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title_fullStr The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title_full_unstemmed The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title_short The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes
title_sort interplay between colon cancer cells and tumour-associated stromal cells impacts the biological clock and enhances malignant phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678177/
https://www.ncbi.nlm.nih.gov/pubmed/31311174
http://dx.doi.org/10.3390/cancers11070988
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