4.7 Article

Enzyme-Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes

期刊

MACROMOLECULAR BIOSCIENCE
卷 17, 期 9, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201700117

关键词

collagen; degradation; extracellular matrix (ECM); hydrogels; matrix metalloproteinases

资金

  1. National Institute of Health [R25 CA154015A]
  2. National Science Foundation [CBET-140349]
  3. National Science Foundation (STC-EBICS) [0939511]
  4. Mayo Clinic
  5. Korean Institute of Science and Technology [2E25498]
  6. National University of Singapore [R279000353112]
  7. Dow Chemical Company
  8. Div Of Chem, Bioeng, Env, & Transp Sys
  9. Directorate For Engineering [1403491] Funding Source: National Science Foundation

向作者/读者索取更多资源

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 approximate to 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.

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