2021 Fiscal Year Annual Research Report
A fludic material-based dynamic cell culture platform as an ex vivo disease model of breast cancer metastasis
| Project/Area Number |
21J10260
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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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| Keywords | Senescence / Surface Fluidity / Cancer Stemness / Quiescence |
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| Outline of Annual Research Achievements |
My research is about elucidating the correlation between the mechanical properties of cell culture substrate and breast cancer cellular fate (senescence and stemness of cancer). By knowing that correlation, I expect to be able to develop a substrate for studying the migration process of breast cancer cells from breast tissue to the other organ. During the first fiscal year, I have been able to confirm a part of the mechanism of the material induced-senescence when culturing the breast cancer cells on the viscous-dominant substrate and which viscous parameters of the substrate is important in determining the fate of breast cancer cells into senescence fate. The surface viscous properties of the substrate, instead of the bulk ones, induce the senescence fate of breast cancer cells on the viscous-dominant substrate, through a series of cell-adhesion protein and involvement of reactive oxygen species. Besides that, I also obtain a preliminary result of the positive correlation between material fluidity-induced senescence and the reactivation of breast cancer cells. The fluidity of the materials induce the senescence of the breast cancer cells which also lead to the reactivation of breast cancer cells when they are grown on the stiffer matrix.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
My research progressed slowly because it took quite a long time to learn new characterization technique for measuring the surface mechanical properties of the fluidic materials, such as by using conventional nano-indenter and AFM. Besides that, it also took quite a long time to finally be able to master the flow cytometry analysis. As for the reversible photocrosslinkable/photocleavable substrate, the pre-liminary synthesis method is in the optimization stage, because a special molecule purification technique is required. Overall, the reason that contributes to the slow progress of my research, is the long time it took for me to master the characterization methods of either the material or cells. Another additional reason is that, I needed to find out the mechanism of the material fluidity-induced senescence in breast cancer cells before investigating about cancer stem cell, and finding out the main pathway of the machanism took some trial/error processes.
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| Strategy for Future Research Activity |
The next step of my research, from the second fiscal year, is about studying the correlation between matrix mechanical properties, cancer metastasis, and drug resistance of the breast cancer cells. It means that I will characterize the behavior of the breast cancer cells on the dynamically photo-tuned substrate. Therefore, I will mainly focus on the synthesis of the photocrosslinkable/photoreversible cell culture substrate and confirming the correlation of the senescence-cancer stemness. After those two goals have been reached, I will decide which stage of the cancer progression I will be focused on, and then perform the drug screening to confirm the drug resistance properties of the breast cancer cells. By performing those steps, I also expect to simultaneously confirming the existence of the breast cancer mechanical memory on the substrate.
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