2017 Fiscal Year Annual Research Report
Unraveling the Mechanism behind Cell Motility Enhancement due to Anisotropic Mechanical Signals in Relation to Cancer and Metastasis
| Project/Area Number |
16H05972
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| Research Institution | The University of Tokyo |
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Principal Investigator |
久代 京一郎 東京大学, 大学院工学系研究科(工学部), 助教 (90632539)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | Cell Migration / Cancer / Microtopography / Mechanotransduction / EMT |
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| Outline of Annual Research Achievements |
In my research to understand the effects of material surface topography on cell motility of normal and cancerous cells, we made a couple interesting discoveries in the fiscal year 2017. With the much appreciated research funding by the Grant-in-Aid of Young Scientists (A), we had purchased and implemented the multi-point incubator-microscope system (AZTEC CCM-1.41IID/C) for cell monitoring, and by utilizing this system, we discovered some intriguing differences between the movement of normal and cancerous cells when they encounter microtopography, which important in cell migration processes like cancer metastasis and EMT. We found that cancerous cells, due to their broken cytoskeletal organization, do not receive strong signals from the microtopographical structures, and this allows them to even completely ignore the structures and climb over them. This is different from the normal cells that align their cytoskeleton to the microtopographical features, polarize and migrate in that direction. Furthermore, we have combined such topographical cues with other forms of directional cues such as fluid flow and chemical gradient, and found that topographical cues seem to dominate over other cues, but there are synergistic effects as well. In addition, we are investigating new types of topography with acute wall angles and observing interesting motility phenomena. The research results thus far have been turned into a paper, published in Journal Nature Scientific Reports in 2017, and we also have more being currently prepared for manuscripts.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The progression of research is mostly in line with what was initially planned, since we have already successfully achieved the identification of key mechanotransduction molecules and understand the underlying mechanotransduction behind the topography-directed cell migration movements. Now, the final goal is to successfully design biodevices that can separate out normal and cancerous cells utilizing these toporaphical cues. We have thus far tried and failed in this regard, mainly because not enough cells would come in contact with the topographical features. Therefore, we are trying to incorporate other forms of directional cues such as flow and chemical gradients so that we can guide the cells to the microgroove topography and thus achieve effective separation. Other than that, the research is overall progressing as planned.
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| Strategy for Future Research Activity |
Basic Research Roadmap
1.We are testing out non-conventional 3D structures involving angled walls (angles ranging from 30-120 degrees) and steps, which may be able to guide certain types of cells to different directions.
2.There are other material and surface properties (such as elasticity and adhesivity) that can affect cell migration, so we are investigating the influence of changing these parameters on the topography-directed cell migration.
3.There are also results to suggest that the topography-induced cell migration behavior switching is related to the EMT phenomenon, which in the current state of research is very difficult and expensive to study, and this topography-based platform may offer a cheap alternative to study EMT. Thus, we are looking for EMT-defining protein expressions in the cells exposed to microtopography for an extended period.
4.We are devising a microdevice to manipulate normal and cancer cells in order to separate them using topography-based cues as a final goal for this project.
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