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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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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. |
format | Online Article Text |
id | pubmed-7524802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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