| Project/Area Number |
21J10260
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 国内 |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
NAJMINA MAZAYA 筑波大学, 理工情報生命学術院, 特別研究員(DC2)
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| Project Period (FY) |
2021-04-28 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2022: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2021: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | stress relaxation time / viscosity / breast cancer cell / molecular weight / low molecular weight / cell cycle arrest / reactive oxygen species / Senescence / Surface Fluidity / Cancer Stemness / Quiescence |
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| Outline of Research at the Start |
This research is conducted to design a poymeric-based substrate for cell culture platform that is able to undergo a reversible dynamic change in term of substrate mechanical properties (soft <-> stiff), to mimic the mechanical change of tissue during the breast cancer disease progression. By performing characterization methods to investigate the change of breast cancer cellular function and fate during the change of substrate mechanical properties, finally, the efficacy of drug treatment on this system would be investigated and compared to the result of the drug testing in the mice.
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| Outline of Annual Research Achievements |
Through culturing the breast cancer cell line (MCF-7) on a viscous-dominant viscoelastic polymer substrate, it was demonstrated that stress relaxation time of the polymeric substrate is the dominant parameter that regulates the cell cycle arrest of non-invasive breast cancer cells. This research firstly reported that breast cancer cells can sense the material relaxation time at the range of milliseconds (80-290 ms). The viscous-dominant polymeric material induced the cellular senescence of breast cancer cellsthrough the generation of reactive oxygen species. Moreover, I was able to demonstrate that we can directly tune the the cellular fate of breast cancer cells by manipulating the molecular properties of the polymer (molecular weight distribution and molecular weight). The intracellular function and growth state of MCF7 cells are able to be manipulated by changing the molecular weight distribution (MWD) of a copolymer. Increasing the MWD (MWD > 1.5) promoted cell populations to form multicellular aggregates due to the decreasing bulk stress relaxation time of the substrate. The presence of low molecular weight polymer which results in MWD > 1.5 can switch the proliferative fate of breast cancer cells (MCF7) into cell cycle arrest fate accompanied by the generation of reactive oxygen species. Through those findings, I was also able to propose a new non-invasive method to distinguish the senescent cells from dormant cells and cells in normal-growth state based on the total protein content of cells through a phase difference by quantitative phase microscopy technique.
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| Research Progress Status |
令和4年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和4年度が最終年度であるため、記入しない。
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