Enzyme-induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypesa

The progression of cancer is often accompanied by changes in the mechanical properties of an extracellular matrix. However, limited efforts have been made to reproduce these biological events in vitro. To this end, this study demonstrates that matrix remodeling caused by matrix metalloproteinase (MM...

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Published inMacromolecular bioscience Vol. 17; no. 9
Main Authors Liang, Youyun, Clay, Nicholas Edwin, Sullivan, Kathryn M., Leong, Jiayu, Ozcelikkale, Altug, Rich, Max H., Lee, Min Kyung, Lai, Mei-Hsiu, Jeon, Hojeong, Han, Bumsoo, Tong, Yen Wah, Kong, Hyunjoon
Format Journal Article
LanguageEnglish
Published 06.07.2017
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Summary:The progression of cancer is often accompanied by changes in the mechanical properties of an extracellular matrix. However, limited efforts have been made to reproduce these biological events in vitro. To this end, this study demonstrates that matrix remodeling caused by matrix metalloproteinase (MMP)-1 regulates phenotypic activities and modulates radiosensitivity of cancer cells exclusively in a 3D matrix. In this study, hepatocarcinoma cells are cultured in a collagen-based gel tailored to present an elastic modulus of approximately 4.0 kPa. The subsequent exposure of the gel to MMP-1 decreases the elastic modulus from 4.0 to 0.5 kPa. In response to MMP-1, liver cancer cells undergo active proliferation, downregulation of E-cadherin and the loss of detoxification capacity. The resulting spheroids are more sensitive to radiation than the spheroids cultured in the stiffer gel not exposed to MMP-1. Overall, this study serves to better understand and control the effects of MMP-induced matrix remodeling.
ISSN:1616-5187
1616-5195
DOI:10.1002/mabi.201700117