Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis.

Papanicolaou, M; Parker, AL; Yam, M; Filipe, EC; Wu, SZ; Chitty, JL; Wyllie, K; Tran, E; Mok, E; Nadalini, A; Skhinas, JN; Lucas, MC; Herrmann, D; Nobis, M; Pereira, BA; Law, AMK; Castillo, L; Murphy, KJ; Zaratzian, A; Hastings, JF; Croucher, DR; Lim, E; Oliver, BG; Mora, FV; Parker, BL; Gallego-Ortega, D; Swarbrick, A; O'Toole, S; Timpson, P; Cox, TR

Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis.

Parker, AL Yam, M Filipe, EC Wu, SZ Chitty, JL Wyllie, K Tran, E Mok, E Nadalini, A Skhinas, JN Lucas, MC Herrmann, D Nobis, M Pereira, BA Law, AMK Castillo, L Murphy, KJ Zaratzian, A Hastings, JF Croucher, DR Lim, E Oliver, BG Mora, FV Parker, BL Gallego-Ortega, D Swarbrick, A O'Toole, S Timpson, P Cox, TR

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2022, 13, (1), pp. 4587
Issue Date:: 2022-08-06

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Field	Value	Language
dc.contributor.author	Papanicolaou, M https://orcid.org/0000-0002-7998-3171
dc.contributor.author	Parker, AL
dc.contributor.author	Yam, M
dc.contributor.author	Filipe, EC
dc.contributor.author	Wu, SZ
dc.contributor.author	Chitty, JL
dc.contributor.author	Wyllie, K
dc.contributor.author	Tran, E
dc.contributor.author	Mok, E
dc.contributor.author	Nadalini, A
dc.contributor.author	Skhinas, JN
dc.contributor.author	Lucas, MC
dc.contributor.author	Herrmann, D
dc.contributor.author	Nobis, M
dc.contributor.author	Pereira, BA
dc.contributor.author	Law, AMK
dc.contributor.author	Castillo, L
dc.contributor.author	Murphy, KJ
dc.contributor.author	Zaratzian, A
dc.contributor.author	Hastings, JF
dc.contributor.author	Croucher, DR
dc.contributor.author	Lim, E
dc.contributor.author	Oliver, BG
dc.contributor.author	Mora, FV
dc.contributor.author	Parker, BL
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Swarbrick, A
dc.contributor.author	O'Toole, S
dc.contributor.author	Timpson, P
dc.contributor.author	Cox, TR
dc.date.accessioned	2023-01-25T03:24:28Z
dc.date.available	2022-07-22
dc.date.available	2023-01-25T03:24:28Z
dc.date.issued	2022-08-06
dc.identifier.citation	Nat Commun, 2022, 13, (1), pp. 4587
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/165429
dc.description.abstract	The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-022-32255-7
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Collagen
dc.subject.mesh	Collagen Type I
dc.subject.mesh	Collagen Type XII
dc.subject.mesh	Extracellular Matrix
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Neoplasm Recurrence, Local
dc.subject.mesh	Proteomics
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Extracellular Matrix
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Neoplasm Recurrence, Local
dc.subject.mesh	Collagen
dc.subject.mesh	Collagen Type I
dc.subject.mesh	Collagen Type XII
dc.subject.mesh	Proteomics
dc.subject.mesh	Female
dc.subject.mesh	Tumor Microenvironment
dc.title	Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-01-25T03:23:29Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	13
utslib.citation.issue	1

Abstract:

The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/165429