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Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma

BACKGROUND: Cancer-associated fibroblasts (CAFs) are highly differentiated and heterogeneous cancer-stromal cells that promote tumour growth, angiogenesis and matrix remodelling. METHODS: We utilised an adapted version of a previously developed 3D in vitro model of colorectal cancer, composed of a c...

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Autores principales: Pape, Judith, Magdeldin, Tarig, Stamati, Katerina, Nyga, Agata, Loizidou, Marilena, Emberton, Mark, Cheema, Umber
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524802/
https://www.ncbi.nlm.nih.gov/pubmed/32641866
http://dx.doi.org/10.1038/s41416-020-0973-9
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author Pape, Judith
Magdeldin, Tarig
Stamati, Katerina
Nyga, Agata
Loizidou, Marilena
Emberton, Mark
Cheema, Umber
author_facet Pape, Judith
Magdeldin, Tarig
Stamati, Katerina
Nyga, Agata
Loizidou, Marilena
Emberton, Mark
Cheema, Umber
author_sort Pape, Judith
collection PubMed
description BACKGROUND: Cancer-associated fibroblasts (CAFs) are highly differentiated and heterogeneous cancer-stromal cells that promote tumour growth, angiogenesis and matrix remodelling. METHODS: We utilised an adapted version of a previously developed 3D in vitro model of colorectal cancer, composed of a cancer mass and the surrounding stromal compartment. We compared cancer invasion with an acellular stromal surround, a “healthy” or normal cellular stroma and a cancerous stroma. For the cancerous stroma, we incorporated six patient-derived CAF samples to study their differential effects on cancer growth, vascular network formation and remodelling. RESULTS: CAFs enhanced the distance and surface area of the invasive cancer mass whilst inhibiting vascular-like network formation. These processes correlated with the upregulation of hepatocyte growth factor (HGF), metallopeptidase inhibitor 1 (TIMP1) and fibulin-5 (FBLN5). Vascular remodelling of previously formed endothelial structures occurred through the disruption of complex networks, and was associated with the upregulation of vascular endothelial growth factor (VEGFA) and downregulation in vascular endothelial cadherin (VE-Cadherin). CONCLUSIONS: These results support, within a biomimetic 3D, in vitro framework, the direct role of CAFs in promoting cancer invasion, and their key function in driving vasculogenesis and angiogenesis.
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spelling pubmed-75248022021-07-09 Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma Pape, Judith Magdeldin, Tarig Stamati, Katerina Nyga, Agata Loizidou, Marilena Emberton, Mark Cheema, Umber Br J Cancer Article BACKGROUND: Cancer-associated fibroblasts (CAFs) are highly differentiated and heterogeneous cancer-stromal cells that promote tumour growth, angiogenesis and matrix remodelling. METHODS: We utilised an adapted version of a previously developed 3D in vitro model of colorectal cancer, composed of a cancer mass and the surrounding stromal compartment. We compared cancer invasion with an acellular stromal surround, a “healthy” or normal cellular stroma and a cancerous stroma. For the cancerous stroma, we incorporated six patient-derived CAF samples to study their differential effects on cancer growth, vascular network formation and remodelling. RESULTS: CAFs enhanced the distance and surface area of the invasive cancer mass whilst inhibiting vascular-like network formation. These processes correlated with the upregulation of hepatocyte growth factor (HGF), metallopeptidase inhibitor 1 (TIMP1) and fibulin-5 (FBLN5). Vascular remodelling of previously formed endothelial structures occurred through the disruption of complex networks, and was associated with the upregulation of vascular endothelial growth factor (VEGFA) and downregulation in vascular endothelial cadherin (VE-Cadherin). CONCLUSIONS: These results support, within a biomimetic 3D, in vitro framework, the direct role of CAFs in promoting cancer invasion, and their key function in driving vasculogenesis and angiogenesis. Nature Publishing Group UK 2020-07-09 2020-09-29 /pmc/articles/PMC7524802/ /pubmed/32641866 http://dx.doi.org/10.1038/s41416-020-0973-9 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Pape, Judith
Magdeldin, Tarig
Stamati, Katerina
Nyga, Agata
Loizidou, Marilena
Emberton, Mark
Cheema, Umber
Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title_full Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title_fullStr Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title_full_unstemmed Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title_short Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
title_sort cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524802/
https://www.ncbi.nlm.nih.gov/pubmed/32641866
http://dx.doi.org/10.1038/s41416-020-0973-9
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