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Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Wullkopf, Lena ; West, Ann-Katrine V ; Leijnse, Natascha ; Cox, Thomas R ; Madsen, Chris D LU ; Oddershede, Lene B and Erler, Janine T (2018) In Molecular Biology of the Cell 29(20). p.2359-2507
Abstract

Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probing the adaptability of cancer cells to altered ECM stiffness using optical tweezers based micro-rheology and deformability cytometry, we find that only malignant cancer cells have the ability to adjust to collagen matrices of different densities. Employing micro-rheology on the biologically relevant spheroid invasion assay, we can furthermore demonstrate that even within a cluster of cells of similar origin there are differences in the... (More)

Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probing the adaptability of cancer cells to altered ECM stiffness using optical tweezers based micro-rheology and deformability cytometry, we find that only malignant cancer cells have the ability to adjust to collagen matrices of different densities. Employing micro-rheology on the biologically relevant spheroid invasion assay, we can furthermore demonstrate that even within a cluster of cells of similar origin there are differences in the intracellular biomechanical properties dependent on the cells' invasive behavior. We reveal a consistent increase of viscosity in cancer cells leading the invasion into the collagen matrices in comparison to cancer cells following in the stalk or remaining in the center of the spheroid. We hypothesize that this differential viscoelasticity might facilitate spheroid tip invasion through a dense matrix. These findings highlight the importance of the biomechanical interplay between cells and their microenvironment for tumor progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Biology of the Cell
volume
29
issue
20
pages
2359 - 2507
publisher
American Society for Cell Biology
external identifiers
  • scopus:85054616103
  • pmid:30091653
ISSN
1939-4586
DOI
10.1091/mbc.E18-05-0319
language
English
LU publication?
yes
id
60b1b878-2891-4b44-8b51-ee1cb1d75999
date added to LUP
2018-09-03 13:59:59
date last changed
2021-10-10 03:18:35
@article{60b1b878-2891-4b44-8b51-ee1cb1d75999,
  abstract     = {<p>Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probing the adaptability of cancer cells to altered ECM stiffness using optical tweezers based micro-rheology and deformability cytometry, we find that only malignant cancer cells have the ability to adjust to collagen matrices of different densities. Employing micro-rheology on the biologically relevant spheroid invasion assay, we can furthermore demonstrate that even within a cluster of cells of similar origin there are differences in the intracellular biomechanical properties dependent on the cells' invasive behavior. We reveal a consistent increase of viscosity in cancer cells leading the invasion into the collagen matrices in comparison to cancer cells following in the stalk or remaining in the center of the spheroid. We hypothesize that this differential viscoelasticity might facilitate spheroid tip invasion through a dense matrix. These findings highlight the importance of the biomechanical interplay between cells and their microenvironment for tumor progression.</p>},
  author       = {Wullkopf, Lena and West, Ann-Katrine V and Leijnse, Natascha and Cox, Thomas R and Madsen, Chris D and Oddershede, Lene B and Erler, Janine T},
  issn         = {1939-4586},
  language     = {eng},
  number       = {20},
  pages        = {2359--2507},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential},
  url          = {http://dx.doi.org/10.1091/mbc.E18-05-0319},
  doi          = {10.1091/mbc.E18-05-0319},
  volume       = {29},
  year         = {2018},
}