Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression
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. Us...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1154528/full |
| _version_ | 1797777684047069184 |
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| author | Maria Rafaeva Adina R. D. Jensen Edward R. Horton Kamilla W. Zornhagen Jan E. Strøbech Lutz Fleischhauer Lutz Fleischhauer Alejandro E. Mayorca-Guiliani Sebastian R. Nielsen Dina S. Grønseth Filip Kuś Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Luis Arnes Manuel Koch Manuel Koch Hauke Clausen-Schaumann Hauke Clausen-Schaumann Valerio Izzi Valerio Izzi Valerio Izzi Raphael Reuten Raphael Reuten Raphael Reuten Janine T. Erler |
| author_facet | Maria Rafaeva Adina R. D. Jensen Edward R. Horton Kamilla W. Zornhagen Jan E. Strøbech Lutz Fleischhauer Lutz Fleischhauer Alejandro E. Mayorca-Guiliani Sebastian R. Nielsen Dina S. Grønseth Filip Kuś Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Luis Arnes Manuel Koch Manuel Koch Hauke Clausen-Schaumann Hauke Clausen-Schaumann Valerio Izzi Valerio Izzi Valerio Izzi Raphael Reuten Raphael Reuten Raphael Reuten Janine T. Erler |
| author_sort | Maria Rafaeva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T23:07:18Z |
| format | Article |
| id | doaj.art-1b359b8013e44394a924f6031f8d7cb2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T23:07:18Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1b359b8013e44394a924f6031f8d7cb22023-07-18T10:53:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11545281154528Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progressionMaria Rafaeva0Adina R. D. Jensen1Edward R. Horton2Kamilla W. Zornhagen3Jan E. Strøbech4Lutz Fleischhauer5Lutz Fleischhauer6Alejandro E. Mayorca-Guiliani7Sebastian R. Nielsen8Dina S. Grønseth9Filip Kuś10Erwin M. Schoof11Erwin M. Schoof12Erwin M. Schoof13Erwin M. Schoof14Luis Arnes15Manuel Koch16Manuel Koch17Hauke Clausen-Schaumann18Hauke Clausen-Schaumann19Valerio Izzi20Valerio Izzi21Valerio Izzi22Raphael Reuten23Raphael Reuten24Raphael Reuten25Janine T. Erler26Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkCenter for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, Munich, GermanyCenter for NanoScience – CsNS, Ludwig-Maximilians-University Munich, Munich, GermanyBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, DenmarkThe Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Centre for Stem Cell Biology, DanStem, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkCenter for Biochemistry, Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyInstitute for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, Munich, GermanyCenter for NanoScience – CsNS, Ludwig-Maximilians-University Munich, Munich, GermanyFaculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland0Faculty of Medicine, University of Oulu, Oulu, Finland1Foundation for the Finnish Cancer Institute, Helsinki, FinlandBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark2Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, Freiburg, Germany3Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, GermanyBiotech Research and Innovation Centre, University of Copenhagen, Copenhagen, DenmarkThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1154528/fullextracellular matrixfibroblastsmechanicsmodelsdesmoplasiapancreatic cancer |
| spellingShingle | Maria Rafaeva Adina R. D. Jensen Edward R. Horton Kamilla W. Zornhagen Jan E. Strøbech Lutz Fleischhauer Lutz Fleischhauer Alejandro E. Mayorca-Guiliani Sebastian R. Nielsen Dina S. Grønseth Filip Kuś Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Erwin M. Schoof Luis Arnes Manuel Koch Manuel Koch Hauke Clausen-Schaumann Hauke Clausen-Schaumann Valerio Izzi Valerio Izzi Valerio Izzi Raphael Reuten Raphael Reuten Raphael Reuten Janine T. Erler Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression Frontiers in Immunology extracellular matrix fibroblasts mechanics models desmoplasia pancreatic cancer |
| title | Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| title_full | Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| title_fullStr | Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| title_full_unstemmed | Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| title_short | Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| title_sort | fibroblast derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression |
| topic | extracellular matrix fibroblasts mechanics models desmoplasia pancreatic cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1154528/full |
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