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Basement membrane s...
Basement membrane stiffness determines metastases formation
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- Reuten, Raphael (author)
- University of Copenhagen
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- Zendehroud, Sina (author)
- Free University of Berlin
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- Nicolau, Monica (author)
- University of Copenhagen
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- Fleischhauer, Lutz (author)
- Munich University of Applied Sciences
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- Laitala, Anu (author)
- University of Copenhagen
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- Kiderlen, Stefanie (author)
- Munich University of Applied Sciences,Ludwig-Maximilian University of Munich
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- Nikodemus, Denise (author)
- University of Copenhagen
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- Wullkopf, Lena (author)
- University of Copenhagen
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- Nielsen, Sebastian Rune (author)
- University of Copenhagen
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- McNeilly, Sarah (author)
- University of Glasgow
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- Prein, Carina (author)
- University of Western Ontario
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- Rafaeva, Maria (author)
- University of Copenhagen
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- Schoof, Erwin M. (author)
- Technical University of Denmark
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- Furtwängler, Benjamin (author)
- University of Copenhagen
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- Porse, Bo T. (author)
- University of Copenhagen
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- Kim, Hyobin (author)
- University of Copenhagen
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- Won, Kyoung Jae (author)
- University of Copenhagen
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- Sudhop, Stefanie (author)
- Ludwig-Maximilian University of Munich
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- Zornhagen, Kamilla Westarp (author)
- University of Copenhagen
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- Suhr, Frank (author)
- Catholic University of Leuven
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- Maniati, Eleni (author)
- Queen Mary University
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- Pearce, Oliver M. T. (author)
- Queen Mary University
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- Koch, Manuel (author)
- University of Cologne,University Hospital of Cologne
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- Oddershede, Lene Broeng (author)
- University of Copenhagen
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- Van Agtmael, Tom (author)
- University of Glasgow
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- Madsen, Chris D. (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancer and matrix remodelling,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Mayorca-Guiliani, Alejandro E. (author)
- University of Copenhagen
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- Bloch, Wilhelm (author)
- German Sport University Cologne
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- Netz, Roland R. (author)
- Free University of Berlin
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- Clausen-Schaumann, Hauke (author)
- Munich University of Applied Sciences,Ludwig-Maximilian University of Munich
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- Erler, Janine T. (author)
- University of Copenhagen
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(creator_code:org_t)
- 2021-01-25
- 2021
- English.
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In: Nature Materials. - : Springer Science and Business Media LLC. - 1476-4660 .- 1476-1122.
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http://dx.doi.org/10...
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Abstract
Subject headings
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- The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores. Our results therefore reveal that BM stiffness is dominant over pore size, and that the mechanical properties of ‘normal’ BMs determine metastases formation and patient survival independent of cancer-mediated alterations. Thus, identifying individual Net4 protein levels within native BMs in major metastatic organs may have the potential to define patient survival even before tumour formation. The ratio of Net4 to laminin molecules determines BM stiffness, such that the more Net4, the softer the BM, thereby decreasing cancer cell invasion activity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Reuten, Raphael
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Zendehroud, Sina
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Nicolau, Monica
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Fleischhauer, Lu ...
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Laitala, Anu
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Kiderlen, Stefan ...
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show more...
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Nikodemus, Denis ...
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Wullkopf, Lena
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Nielsen, Sebasti ...
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McNeilly, Sarah
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Prein, Carina
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Rafaeva, Maria
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Schoof, Erwin M.
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Furtwängler, Ben ...
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Porse, Bo T.
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Kim, Hyobin
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Won, Kyoung Jae
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Sudhop, Stefanie
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Zornhagen, Kamil ...
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Suhr, Frank
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Maniati, Eleni
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Pearce, Oliver M ...
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Koch, Manuel
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Oddershede, Lene ...
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Van Agtmael, Tom
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Madsen, Chris D.
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Mayorca-Guiliani ...
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Bloch, Wilhelm
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Netz, Roland R.
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Clausen-Schauman ...
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Erler, Janine T.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Nature Materials
- By the university
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Lund University