TY - JOUR
T1 - Enzyme-Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes
AU - Liang, Youyun
AU - Clay, Nicholas Edwin
AU - Sullivan, Kathryn M.
AU - Leong, Jiayu
AU - Ozcelikkale, Altug
AU - Rich, Max H.
AU - Lee, Min Kyung
AU - Lai, Mei Hsiu
AU - Jeon, Hojeong
AU - Han, Bumsoo
AU - Tong, Yen Wah
AU - Kong, Hyunjoon
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - collagen
KW - degradation
KW - extracellular matrix (ECM)
KW - hydrogels
KW - matrix metalloproteinases
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U2 - 10.1002/mabi.201700117
DO - 10.1002/mabi.201700117
M3 - Article
C2 - 28683186
AN - SCOPUS:85021783220
SN - 1616-5187
VL - 17
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 9
M1 - 1700117
ER -