Basement membrane stiffness determines metastases formation

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

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Basement membrane stiffness determines metastases formation. / Reuten, Raphael; Zendehroud, Sina; Nicolau, Monica; Fleischhauer, Lutz; Laitala, Anu; Kiderlen, Stefanie; Nikodemus, Denise; Wullkopf, Lena; Nielsen, Sebastian Rune; Mcneilly, Sarah; Prein, Carina; Rafaeva, Maria; Schoof, Erwin M.; Furtwängler, Benjamin; Porse, Bo T.; Kim, Hyobin; Won, Kyoung Jae; Sudhop, Stefanie; Zornhagen, Kamilla Westarp; Suhr, Frank; Maniati, Eleni; Pearce, Oliver M. T.; Koch, Manuel; Oddershede, Lene Broeng; Van Agtmael, Tom; Madsen, Chris D.; Mayorca-guiliani, Alejandro E.; Bloch, Wilhelm; Netz, Roland R.; Clausen-schaumann, Hauke; Erler, Janine T.

I: Nature Materials, Bind 20, 2021, s. 892–903.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Reuten, R, Zendehroud, S, Nicolau, M, Fleischhauer, L, Laitala, A, Kiderlen, S, Nikodemus, D, Wullkopf, L, Nielsen, SR, Mcneilly, S, Prein, C, Rafaeva, M, Schoof, EM, Furtwängler, B, Porse, BT, Kim, H, Won, KJ, Sudhop, S, Zornhagen, KW, Suhr, F, Maniati, E, Pearce, OMT, Koch, M, Oddershede, LB, Van Agtmael, T, Madsen, CD, Mayorca-guiliani, AE, Bloch, W, Netz, RR, Clausen-schaumann, H & Erler, JT 2021, 'Basement membrane stiffness determines metastases formation', Nature Materials, bind 20, s. 892–903. https://doi.org/10.1038/s41563-020-00894-0

APA

Reuten, R., Zendehroud, S., Nicolau, M., Fleischhauer, L., Laitala, A., Kiderlen, S., Nikodemus, D., Wullkopf, L., Nielsen, S. R., Mcneilly, S., Prein, C., Rafaeva, M., Schoof, E. M., Furtwängler, B., Porse, B. T., Kim, H., Won, K. J., Sudhop, S., Zornhagen, K. W., ... Erler, J. T. (2021). Basement membrane stiffness determines metastases formation. Nature Materials, 20, 892–903. https://doi.org/10.1038/s41563-020-00894-0

Vancouver

Reuten R, Zendehroud S, Nicolau M, Fleischhauer L, Laitala A, Kiderlen S o.a. Basement membrane stiffness determines metastases formation. Nature Materials. 2021;20:892–903. https://doi.org/10.1038/s41563-020-00894-0

Author

Reuten, Raphael ; Zendehroud, Sina ; Nicolau, Monica ; Fleischhauer, Lutz ; Laitala, Anu ; Kiderlen, Stefanie ; Nikodemus, Denise ; Wullkopf, Lena ; Nielsen, Sebastian Rune ; Mcneilly, Sarah ; Prein, Carina ; Rafaeva, Maria ; Schoof, Erwin M. ; Furtwängler, Benjamin ; Porse, Bo T. ; Kim, Hyobin ; Won, Kyoung Jae ; Sudhop, Stefanie ; Zornhagen, Kamilla Westarp ; Suhr, Frank ; Maniati, Eleni ; Pearce, Oliver M. T. ; Koch, Manuel ; Oddershede, Lene Broeng ; Van Agtmael, Tom ; Madsen, Chris D. ; Mayorca-guiliani, Alejandro E. ; Bloch, Wilhelm ; Netz, Roland R. ; Clausen-schaumann, Hauke ; Erler, Janine T. / Basement membrane stiffness determines metastases formation. I: Nature Materials. 2021 ; Bind 20. s. 892–903.

Bibtex

@article{301b723acd1748a7a5eabdbc1316921f,
title = "Basement membrane stiffness determines metastases formation",
abstract = "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 {\textquoteleft}normal{\textquoteright} 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.",
author = "Raphael Reuten and Sina Zendehroud and Monica Nicolau and Lutz Fleischhauer and Anu Laitala and Stefanie Kiderlen and Denise Nikodemus and Lena Wullkopf and Nielsen, {Sebastian Rune} and Sarah Mcneilly and Carina Prein and Maria Rafaeva and Schoof, {Erwin M.} and Benjamin Furtw{\"a}ngler and Porse, {Bo T.} and Hyobin Kim and Won, {Kyoung Jae} and Stefanie Sudhop and Zornhagen, {Kamilla Westarp} and Frank Suhr and Eleni Maniati and Pearce, {Oliver M. T.} and Manuel Koch and Oddershede, {Lene Broeng} and {Van Agtmael}, Tom and Madsen, {Chris D.} and Mayorca-guiliani, {Alejandro E.} and Wilhelm Bloch and Netz, {Roland R.} and Hauke Clausen-schaumann and Erler, {Janine T.}",
year = "2021",
doi = "10.1038/s41563-020-00894-0",
language = "English",
volume = "20",
pages = "892–903",
journal = "Nature Materials",
issn = "1476-1122",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Basement membrane stiffness determines metastases formation

AU - Reuten, Raphael

AU - Zendehroud, Sina

AU - Nicolau, Monica

AU - Fleischhauer, Lutz

AU - Laitala, Anu

AU - Kiderlen, Stefanie

AU - Nikodemus, Denise

AU - Wullkopf, Lena

AU - Nielsen, Sebastian Rune

AU - Mcneilly, Sarah

AU - Prein, Carina

AU - Rafaeva, Maria

AU - Schoof, Erwin M.

AU - Furtwängler, Benjamin

AU - Porse, Bo T.

AU - Kim, Hyobin

AU - Won, Kyoung Jae

AU - Sudhop, Stefanie

AU - Zornhagen, Kamilla Westarp

AU - Suhr, Frank

AU - Maniati, Eleni

AU - Pearce, Oliver M. T.

AU - Koch, Manuel

AU - Oddershede, Lene Broeng

AU - Van Agtmael, Tom

AU - Madsen, Chris D.

AU - Mayorca-guiliani, Alejandro E.

AU - Bloch, Wilhelm

AU - Netz, Roland R.

AU - Clausen-schaumann, Hauke

AU - Erler, Janine T.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41563-020-00894-0

DO - 10.1038/s41563-020-00894-0

M3 - Journal article

C2 - 33495631

VL - 20

SP - 892

EP - 903

JO - Nature Materials

JF - Nature Materials

SN - 1476-1122

ER -

ID: 255784050