EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion

Summary: Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here, we addressed this question by performing 3D spheroid invasion assays on epithel...

Full description

Saved in:
Bibliographic Details
Main Authors: Anouk van der Net, Zaid Rahman, Ankur D. Bordoloi, Iain Muntz, Peter ten Dijke, Pouyan E. Boukany, Gijsje H. Koenderink
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422402649X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846113136875143168
author Anouk van der Net
Zaid Rahman
Ankur D. Bordoloi
Iain Muntz
Peter ten Dijke
Pouyan E. Boukany
Gijsje H. Koenderink
author_facet Anouk van der Net
Zaid Rahman
Ankur D. Bordoloi
Iain Muntz
Peter ten Dijke
Pouyan E. Boukany
Gijsje H. Koenderink
author_sort Anouk van der Net
collection DOAJ
description Summary: Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here, we addressed this question by performing 3D spheroid invasion assays on epithelial-like (A549) and mesenchymal-like (MV3) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells and matrix porosity. We found that the onset time of invasion was correlated with the matrix porosity and vimentin levels, while the spheroid expansion rate correlated with MMP1 levels. Spheroids displayed solid-like (non-invasive) states in small-pore hydrogels and fluid-like (strand-based) or gas-like (disseminating cells) states in large-pore hydrogels or for mesenchymal-like cells. Our findings are consistent with different unjamming states as a function of cell motility and matrix confinement predicted in recent models for cancer invasion, but show that cell motility and matrix confinement are coupled via EMT-related matrix degradation.
format Article
id doaj-art-484aae2e6b1d490a82a5331aa6ff987d
institution Kabale University
issn 2589-0042
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-484aae2e6b1d490a82a5331aa6ff987d2024-12-22T05:29:19ZengElsevieriScience2589-00422024-12-012712111424EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasionAnouk van der Net0Zaid Rahman1Ankur D. Bordoloi2Iain Muntz3Peter ten Dijke4Pouyan E. Boukany5Gijsje H. Koenderink6Delft University of Technology, Department of Bionanoscience, Kavli Institute of Nanoscience, Delft 2629 HZ, the NetherlandsDelft University of Technology, Department of Chemical Engineering, Delft 2629 HZ, the NetherlandsDelft University of Technology, Department of Chemical Engineering, Delft 2629 HZ, the NetherlandsDelft University of Technology, Department of Bionanoscience, Kavli Institute of Nanoscience, Delft 2629 HZ, the NetherlandsLeiden University Medical Center, Department of Cell and Chemical Biology and Oncode Institute, Leiden 2333 ZC, the NetherlandsDelft University of Technology, Department of Chemical Engineering, Delft 2629 HZ, the Netherlands; Corresponding authorDelft University of Technology, Department of Bionanoscience, Kavli Institute of Nanoscience, Delft 2629 HZ, the Netherlands; Corresponding authorSummary: Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here, we addressed this question by performing 3D spheroid invasion assays on epithelial-like (A549) and mesenchymal-like (MV3) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells and matrix porosity. We found that the onset time of invasion was correlated with the matrix porosity and vimentin levels, while the spheroid expansion rate correlated with MMP1 levels. Spheroids displayed solid-like (non-invasive) states in small-pore hydrogels and fluid-like (strand-based) or gas-like (disseminating cells) states in large-pore hydrogels or for mesenchymal-like cells. Our findings are consistent with different unjamming states as a function of cell motility and matrix confinement predicted in recent models for cancer invasion, but show that cell motility and matrix confinement are coupled via EMT-related matrix degradation.http://www.sciencedirect.com/science/article/pii/S258900422402649XBiophysicsBiomechanicsCancer
spellingShingle Anouk van der Net
Zaid Rahman
Ankur D. Bordoloi
Iain Muntz
Peter ten Dijke
Pouyan E. Boukany
Gijsje H. Koenderink
EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
iScience
Biophysics
Biomechanics
Cancer
title EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
title_full EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
title_fullStr EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
title_full_unstemmed EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
title_short EMT-related cell-matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
title_sort emt related cell matrix interactions are linked to states of cell unjamming in cancer spheroid invasion
topic Biophysics
Biomechanics
Cancer
url http://www.sciencedirect.com/science/article/pii/S258900422402649X
work_keys_str_mv AT anoukvandernet emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT zaidrahman emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT ankurdbordoloi emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT iainmuntz emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT petertendijke emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT pouyaneboukany emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion
AT gijsjehkoenderink emtrelatedcellmatrixinteractionsarelinkedtostatesofcellunjammingincancerspheroidinvasion