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Enzyme‐Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes
Author(s) -
Liang Youyun,
Clay Nicholas Edwin,
Sullivan Kathryn M.,
Leong Jiayu,
Ozcelikkale Altug,
Rich Max H.,
Lee Min Kyung,
Lai MeiHsiu,
Jeon Hojeong,
Han Bumsoo,
Tong Yen Wah,
Kong Hyunjoon
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700117
Subject(s) - extracellular matrix , cancer cell , matrix metalloproteinase , downregulation and upregulation , chemistry , matrix (chemical analysis) , microbiology and biotechnology , spheroid , in vitro , cancer , phenotype , biophysics , cancer research , biochemistry , biology , chromatography , gene , genetics
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 ≈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.