Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
(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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- author
- Wullkopf, Lena ; West, Ann-Katrine V ; Leijnse, Natascha ; Cox, Thomas R ; Madsen, Chris D LU ; Oddershede, Lene B and Erler, Janine T
- organization
- publishing date
- 2018
- 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
- 2024-07-08 18:14:04
@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}}, }