Matrix rigidity regulates cancer cell growth and cellular phenotype

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

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Background: 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. Methodology/Principal Findings: 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 Ecadherin and decreasing the expression of the mesenchymal transcription factor Slug. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere12905
JournalPLoS One
Volume5
Issue number9
DOIs
StatePublished - 2010
Externally publishedYes

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Cell growth
Rigidity
cell growth
Cells
extracellular matrix
gels
mechanical properties
Phenotype
phenotype
cell lines
Growth
Extracellular Matrix
Neoplasms
Gels
lungs
Stiffness
Cell Line
Mechanical properties
slugs
polyacrylamide

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tilghman, R. W., Cowan, C. R., Mih, J. D., Koryakina, Y., Gioeli, D., Slack-Davis, J. K., ... Parsons, J. T. (2010). Matrix rigidity regulates cancer cell growth and cellular phenotype. PLoS One, 5(9), [e12905]. https://doi.org/10.1371/journal.pone.0012905

Matrix rigidity regulates cancer cell growth and cellular phenotype. / Tilghman, Robert W.; Cowan, Catharine R.; Mih, Justin D.; Koryakina, Yulia; Gioeli, Daniel; Slack-Davis, Jill K.; Blackman, Brett R.; Tschumperlin, Daniel J; Parsons, J. Thomas.

In: PLoS One, Vol. 5, No. 9, e12905, 2010.

Research output: Contribution to journalArticle

Tilghman, RW, Cowan, CR, Mih, JD, Koryakina, Y, Gioeli, D, Slack-Davis, JK, Blackman, BR, Tschumperlin, DJ & Parsons, JT 2010, 'Matrix rigidity regulates cancer cell growth and cellular phenotype', PLoS One, vol. 5, no. 9, e12905. https://doi.org/10.1371/journal.pone.0012905
Tilghman RW, Cowan CR, Mih JD, Koryakina Y, Gioeli D, Slack-Davis JK et al. Matrix rigidity regulates cancer cell growth and cellular phenotype. PLoS One. 2010;5(9). e12905. https://doi.org/10.1371/journal.pone.0012905
Tilghman, Robert W. ; Cowan, Catharine R. ; Mih, Justin D. ; Koryakina, Yulia ; Gioeli, Daniel ; Slack-Davis, Jill K. ; Blackman, Brett R. ; Tschumperlin, Daniel J ; Parsons, J. Thomas. / Matrix rigidity regulates cancer cell growth and cellular phenotype. In: PLoS One. 2010 ; Vol. 5, No. 9.
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