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MATRICAN SIGNED

Matrix during cancer progression

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

MATRICAN project word cloud

Explore the words cloud of the MATRICAN project. It provides you a very rough idea of what is the project "MATRICAN" about.

clinic samples live mouse tumour breaking lack pancreatic validate composition ground situ imaging progression fundamental models spectrometry metastatic intact orthotopic mice marked lines upregulated structurally validation regulates evolution metastasis repopulated discovered play quantitative cellular deaths components stages cells responsible scaffolds ecm impacts tumours subsequent proteins fibrillogenesis extracellular organs breast decrease erc patients pathological cancer translated relevance tissue interactions repopulation human disease perturbation strategies proteomics patient mapping decellularise biochemical alterations transgenic normal primary combat 3d structural global leaving driving critical stiffness mass lab 90 functional matrix spatio benefit structure drive ms cell bearing

Project "MATRICAN" data sheet

The following table provides information about the project.

Coordinator	KOBENHAVNS UNIVERSITET Organization address address: NORREGADE 10 city: KOBENHAVN postcode: 1165 website: www.ku.dk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Denmark [DK]
Project website	https://erlerlab.com/matrican/
Total cost	1˙997˙500 €
EC max contribution	1˙997˙500 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-CoG
Funding Scheme	ERC-COG
Starting year	2016
Duration (year-month-day)	from 2016-09-01 to 2021-08-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KOBENHAVNS UNIVERSITET KOBENHAVNS UNIVERSITET Organization address address: NORREGADE 10 city: KOBENHAVN postcode: 1165 website: www.ku.dk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DK (KOBENHAVN)	coordinator	1˙997˙500.00

Map

Project objective

The extracellular matrix (ECM) is known to play a critical role in driving cancer progression, and yet we lack knowledge of its composition and structure. The goal of my ERC project is to investigate how alterations in biochemical composition and structural properties of the ECM during cancer progression impact on cell behaviour to drive metastasis, which is responsible for over 90% of cancer patient deaths. In order to do this, my lab has developed a method to in situ decellularise organs leaving structurally intact ECM scaffolds for subsequent analysis or for repopulation to study cell-ECM interactions in situ. We have deployed our method to decellularise primary tumour and metastatic organs in mice bearing orthotopic breast cancer tumours for subsequent quantitative global mass spectrometry (MS) proteomics, spatio-structural mapping of ECM components in 3D, and live imaging of repopulated cells. We observed fundamental alterations in ECM composition and structure between normal and tumour, and primary and metastatic tissue. We have selected two ECM components specifically upregulated in metastatic organs for subsequent validation. We discovered a marked decrease in proteins associated with fibrillogenesis in metastatic organs and will investigate the impact of this on metastatic ECM stiffness. We will decellularise organs from transgenic mouse models of breast and pancreatic cancer, at specific stages during cancer progression to determine the evolution of global ECM composition and structure, and how this impacts on cell behaviour through functional perturbation. Finally, we shall validate relevance of findings to human disease through use of human cancer lines and analysis of human patient samples. The research proposed will provide ground-breaking insight into how the ECM regulates cellular behaviour during normal and pathological conditions, and will test new strategies to combat metastasis that could be translated into the clinic to benefit cancer patients.

Publications

List of publications.
year	authors and title	journal	last update
2019	Alejandro E Mayorca-Guiliani, Oliver Willacy, Chris D. Madsen, Maria Rafaeva, Stefanie Elisabeth HeumÃ¼ller, Felix Bock, Gerhard Sengle, Manuel Koch, Thomas Imhof, Frank Zaucke, Raimund Wagener, Takako Sasaki, Janine T. Erler, Raphael Reuten Decellularization and antibody staining of mouse tissues to map native extracellular matrix structures in 3D published pages: , ISSN: 1754-2189, DOI: 10.1038/s41596-019-0225-8	Nature Protocols	2019-11-14
2019	Ulrich Blache, Edward R Horton, Tian Xia, Erwin M Schoof, Lene H Blicher, Angelina SchÃ¶nenberger, Jess G Snedeker, Ivan Martin, Janine T Erler, Martin Ehrbar Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments published pages: e201900304, ISSN: 2575-1077, DOI: 10.26508/lsa.201900304	Life Science Alliance 2/3	2019-08-06

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