University of Oulu

Rafaeva M, Jensen ARD, Horton ER, Zornhagen KW, Strøbech JE, Fleischhauer L, Mayorca-Guiliani AE, Nielsen SR, Grønseth DS, Kuś F, Schoof EM, Arnes L, Koch M, Clausen-Schaumann H, Izzi V, Reuten R and Erler JT (2023) Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression. Front. Immunol. 14:1154528. doi: 10.3389/fimmu.2023.1154528

Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression

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Author: Rafaeva, Maria1; Jensen, Adina R. D.1; Horton, Edward R.1;
Organizations: 1Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
2Center for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, Munich, Germany
3Center for NanoScience – CsNS, Ludwig-Maximilians-University Munich, Munich, Germany
4Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
5The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
6Novo Nordisk Foundation Centre for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
7Center for Biochemistry, Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
8Institute for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
9Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
10Faculty of Medicine, University of Oulu, Oulu, Finland
11Foundation for the Finnish Cancer Institute, Helsinki, Finland
12Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, Freiburg, Germany
13Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.5 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-10-24


The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 14
Article number: 1154528
DOI: 10.3389/fimmu.2023.1154528
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by a PhD fellowship from the Lundbeck Foundation (MR: R286-2018-621), the Danish Council for Independent Research YDUN grant (AJ; 1084181001), the European Research Council (MR, AJ, EH, JS, AM-G, SN, RR, JE: ERC-2015-CoG-682881-MATRICAN), the Danish Cancer Society (SN: R167-A10618; EH: R204-A12445; RR: R204-A12454), the European Molecular Biology Organization (EH: ALTF 922-2016), a Novo Nordisk Foundation Hallas Møller Stipend (JE), and the German Cancer Aid (RR). LF and HC-S acknowledge funding from the Bavarian State Ministry for Science and Art through the Research Focus “Angewandte Photonik” and the Bavarian Academic Forum (BayWISS)—Doctoral Consortium “Health Research”. The Cancer Society of Finland (VI: 63-6445) (VI). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Copyright information: © 2023 Rafaeva, Jensen, Horton, Zornhagen, Strøbech, Fleischhauer, Mayorca-Guiliani, Nielsen, Grønseth, Kuś, Schoof, Arnes, Koch, Clausen-Schaumann, Izzi, Reuten and Erler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.