Impact of extracellular matrix stiffness on cancer cell function and stem cell fate
[thesis]
Yan Li, Universitätsbibliothek Der FU Berlin
2020
Generally, in this thesis, we studied the effect of diverse mechanical environments including different extracellular matrix stiffness and varied hydrogel elasticity on the behaviors and functions of cancer cells and stem cells. Specifically, two topics are included in this thesis. In the first topic, the impacts of 2D substrate stiffness on the cancer stem cell (CSC) maintenance, chemotherapeutic response and autophagy activation in breast cancer cells was investigated. While in the second
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... c, we focused on the impact of the 3D environment and hydrogel elasticity on the proliferation and self-renewal ability of mouse iPS cells. Taken together, no matter culturing on 2D substrates or encapsulating in 3D hydrogels, the mechanical environment provided by extracellular matrix indeed makes a great influence on the phenotypes and gene expressions in either cancer cells or stem cells. In the first project, to study the impact of extracellular matrices stiffness on breast cancer cell functions, we used FN coated polyacrylamide hydrogels as substrates to culture breast cancer cells. By adjusting the ratio and concentration of acrylamide and bis-acrylamide, we fabricated three different elastic substrates with elasticity of ~0.48 kPa, ~4.47 kPa, ~34.88 kPa, which I named "soft" "median" "stiff" substrate. First, we showed the diversity of cellular morphology of MCF-7 cells on different substrates, which is consistent with the previous studies. Cells spread widely on stiff substrate while barely spread on soft one, which may be the main cause of increasing proliferating capacity along with the increased stiffness. Next, we found the different chemotherapeutic response of breast cancer cells on different substrates. Breast cancer cells showed enhanced chemosensitivity to doxorubicin and cisplatin but not cyclophosphamide when matrix stiffness increased. To figure out the main reason for matrix stiffness-dependent different chemotherapy response, we detected the stemness characteristics of breast cancer cells on different [...]
doi:10.17169/refubium-26945
fatcat:rh3s2guc2nb6pdakj3bbl7mfa4