A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion

Summary: Guided by a multi-level “deconstruction” of omental metastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human met...

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Main Authors:	Beatrice Malacrida, Sam Nichols, Eleni Maniati, Roanne Jones, Robin Delanie-Smith, Reza Roozitalab, Eleanor J. Tyler, Morgan Thomas, Gina Boot, Jonas Mackerodt, Michelle Lockley, Martin M. Knight, Frances R. Balkwill, Oliver M.T. Pearce
Format:	Article
Language:	English
Published:	Elsevier 2021-06-01
Series:	iScience
Subjects:	biological sciences cancer systems biology cell biology methodology in biological sciences molecular biology
Online Access:	http://www.sciencedirect.com/science/article/pii/S2589004221006441

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spelling	doaj-99a346004e8b4e63bd0a6643a5d15ba82021-06-27T04:39:36ZengElsevieriScience2589-00422021-06-01246102676A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasionBeatrice Malacrida0Sam Nichols1Eleni Maniati2Roanne Jones3Robin Delanie-Smith4Reza Roozitalab5Eleanor J. Tyler6Morgan Thomas7Gina Boot8Jonas Mackerodt9Michelle Lockley10Martin M. Knight11Frances R. Balkwill12Oliver M.T. Pearce13Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK; School of Engineering and Materials Science, Queen Mary University of London, Mile End, London E1 4NS, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKSchool of Engineering and Materials Science, Queen Mary University of London, Mile End, London E1 4NS, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UKBarts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK; Corresponding authorSummary: Guided by a multi-level “deconstruction” of omental metastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human metastases and allowed malignant cell invasion into the artificial omental structure. Prompted by findings in patient biopsies, we used the model to investigate the role of platelets in malignant cell invasion and extracellular matrix, ECM, production. RNA (sequencing and quantitative polymerase-chain reaction), protein (proteomics and immunohistochemistry) and image analysis revealed that platelets stimulated malignant cell invasion and production of ECM molecules associated with poor prognosis. Moreover, we found that platelet activation of mesothelial cells was critical in stimulating malignant cell invasion. Whilst platelets likely activate both malignant cells and mesothelial cells, the tetra-culture model allowed us to dissect the role of both cell types and model the early stages of HGSOC metastases.http://www.sciencedirect.com/science/article/pii/S2589004221006441biological sciencescancer systems biologycell biologymethodology in biological sciencesmolecular biology
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Beatrice Malacrida Sam Nichols Eleni Maniati Roanne Jones Robin Delanie-Smith Reza Roozitalab Eleanor J. Tyler Morgan Thomas Gina Boot Jonas Mackerodt Michelle Lockley Martin M. Knight Frances R. Balkwill Oliver M.T. Pearce
spellingShingle	Beatrice Malacrida Sam Nichols Eleni Maniati Roanne Jones Robin Delanie-Smith Reza Roozitalab Eleanor J. Tyler Morgan Thomas Gina Boot Jonas Mackerodt Michelle Lockley Martin M. Knight Frances R. Balkwill Oliver M.T. Pearce A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion iScience biological sciences cancer systems biology cell biology methodology in biological sciences molecular biology
author_facet	Beatrice Malacrida Sam Nichols Eleni Maniati Roanne Jones Robin Delanie-Smith Reza Roozitalab Eleanor J. Tyler Morgan Thomas Gina Boot Jonas Mackerodt Michelle Lockley Martin M. Knight Frances R. Balkwill Oliver M.T. Pearce
author_sort	Beatrice Malacrida
title	A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
title_short	A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
title_full	A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
title_fullStr	A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
title_full_unstemmed	A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
title_sort	human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion
publisher	Elsevier
series	iScience
issn	2589-0042
publishDate	2021-06-01
description	Summary: Guided by a multi-level “deconstruction” of omental metastases, we developed a tetra (four cell)-culture model of primary human mesothelial cells, fibroblasts, adipocytes, and high-grade serous ovarian cancer (HGSOC) cell lines. This multi-cellular model replicated key elements of human metastases and allowed malignant cell invasion into the artificial omental structure. Prompted by findings in patient biopsies, we used the model to investigate the role of platelets in malignant cell invasion and extracellular matrix, ECM, production. RNA (sequencing and quantitative polymerase-chain reaction), protein (proteomics and immunohistochemistry) and image analysis revealed that platelets stimulated malignant cell invasion and production of ECM molecules associated with poor prognosis. Moreover, we found that platelet activation of mesothelial cells was critical in stimulating malignant cell invasion. Whilst platelets likely activate both malignant cells and mesothelial cells, the tetra-culture model allowed us to dissect the role of both cell types and model the early stages of HGSOC metastases.
topic	biological sciences cancer systems biology cell biology methodology in biological sciences molecular biology
url	http://www.sciencedirect.com/science/article/pii/S2589004221006441
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A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion

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