Matrix rigidity regulates cancer cell growth and cellular phenotype.
<h4>Background</h4>The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness) of the microenvironment and how t...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012905&type=printable |
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| author | Robert W Tilghman Catharine R Cowan Justin D Mih Yulia Koryakina Daniel Gioeli Jill K Slack-Davis Brett R Blackman Daniel J Tschumperlin J Thomas Parsons |
| author_facet | Robert W Tilghman Catharine R Cowan Justin D Mih Yulia Koryakina Daniel Gioeli Jill K Slack-Davis Brett R Blackman Daniel J Tschumperlin J Thomas Parsons |
| author_sort | Robert W Tilghman |
| collection | DOAJ |
| description | <h4>Background</h4>The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness) of the microenvironment and how this response varies among cancer cell lines.<h4>Methodology/principal findings</h4>In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased), and "rigidity independent" (those which grow equally on both soft and stiff substrates). Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug.<h4>Conclusions/significance</h4>These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models. |
| format | Article |
| id | doaj-art-4a8c02aa9e524f6f874edcd48cd9d95d |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4a8c02aa9e524f6f874edcd48cd9d95d2025-08-20T03:07:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-0159e1290510.1371/journal.pone.0012905Matrix rigidity regulates cancer cell growth and cellular phenotype.Robert W TilghmanCatharine R CowanJustin D MihYulia KoryakinaDaniel GioeliJill K Slack-DavisBrett R BlackmanDaniel J TschumperlinJ Thomas Parsons<h4>Background</h4>The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness) of the microenvironment and how this response varies among cancer cell lines.<h4>Methodology/principal findings</h4>In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased), and "rigidity independent" (those which grow equally on both soft and stiff substrates). Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug.<h4>Conclusions/significance</h4>These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012905&type=printable |
| spellingShingle | Robert W Tilghman Catharine R Cowan Justin D Mih Yulia Koryakina Daniel Gioeli Jill K Slack-Davis Brett R Blackman Daniel J Tschumperlin J Thomas Parsons Matrix rigidity regulates cancer cell growth and cellular phenotype. PLoS ONE |
| title | Matrix rigidity regulates cancer cell growth and cellular phenotype. |
| title_full | Matrix rigidity regulates cancer cell growth and cellular phenotype. |
| title_fullStr | Matrix rigidity regulates cancer cell growth and cellular phenotype. |
| title_full_unstemmed | Matrix rigidity regulates cancer cell growth and cellular phenotype. |
| title_short | Matrix rigidity regulates cancer cell growth and cellular phenotype. |
| title_sort | matrix rigidity regulates cancer cell growth and cellular phenotype |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012905&type=printable |
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