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2017 年度 実績報告書

Unraveling the Mechanism behind Cell Motility Enhancement due to Anisotropic Mechanical Signals in Relation to Cancer and Metastasis

研究課題

研究課題/領域番号 16H05972
研究機関東京大学

研究代表者

久代 京一郎  東京大学, 大学院工学系研究科(工学部), 助教 (90632539)

研究期間 (年度) 2016-04-01 – 2020-03-31
キーワードCell Migration / Cancer / Microtopography / Mechanotransduction / EMT
研究実績の概要

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.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

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.

今後の研究の推進方策

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.

  • 研究成果

    (11件)

すべて 2018 2017

すべて 雑誌論文 (4件) (うち国際共著 2件、 査読あり 2件、 オープンアクセス 1件) 学会発表 (7件) (うち国際学会 4件、 招待講演 3件)

  • [雑誌論文] Fabrication and assessment of an electrospun polymeric microfiber-based platform under bulk flow conditions with rapid and efficient antigen capture2018

    • 著者名/発表者名
      Carlton F. O. Hoy, Keiichiro Kushiro, Madoka Takai
    • 雑誌名

      Analyst

      巻: 143 ページ: 865-873

    • DOI

      10.1039/C8AN90024H

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Differences in Three-Dimensional Geometric Recognition by Non-Cancerous and Cancerous Epithelial Cells on Microgroove-Based Topography2017

    • 著者名/発表者名
      Kushiro K, Yaginuma T, Ryo A, Takai M
    • 雑誌名

      Scientific Reports

      巻: 7 ページ: 4244

    • DOI

      10.1038/s41598-017-03779-6

    • 査読あり / 国際共著
  • [雑誌論文] Influence of Fluid Flow on Microtopography-Guided Cell Migration and Underlying Mechanotransduction2017

    • 著者名/発表者名
      K. Kushiro, A. Ryo, M. Takai
    • 雑誌名

      MicroTAS 2017 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences

      巻: 1 ページ: 830-831

  • [雑誌論文] Single Cell Resolution Analysis of Ultrasound-Produced Multi-Cellular Tumor Spheroids2017

    • 著者名/発表者名
      K. Olofsson, V. Carannante, T. Frisk, K. Kushiro, M. Takai, A. Lunduist, B. Onfelt, M. Wiklund
    • 雑誌名

      MicroTAS 2017 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences

      巻: 1 ページ: 955-956

  • [学会発表] Influence of Fluid Flow on Microtopography-Guided Cell Migration and Underlying Mechanotransduction2017

    • 著者名/発表者名
      K. Kushiro, A. Ryo, M. Takai
    • 学会等名
      MicroTAS 2017 (Savannah, Georgia, USA)
    • 国際学会
  • [学会発表] Single Cell Resolution Analysis of Ultrasound-Produced Multi-Cellular Tumor Spheroids2017

    • 著者名/発表者名
      K. Olofsson, V. Carannante, T. Frisk, K. Kushiro, M. Takai, A. Lunduist, B. Onfelt, M. Wiklund
    • 学会等名
      MicroTAS 2017 (Savannah, Georgia, USA)
    • 国際学会
  • [学会発表] TOPOGRAPHICAL SYSTEMS FOR SINGLE-CELL MIGRATION ANALYSIS TO DISTINGUISH NORMAL AND CANCEROUS CELL TYPES2017

    • 著者名/発表者名
      K. Kushiro, A. Ryo, M. Takai
    • 学会等名
      AIBBC 2017 (Nairobi, Kenya)
    • 国際学会 / 招待講演
  • [学会発表] Effect of Biomaterial Surface Structures and Material Properties on Topography-Driven Cell Migration2017

    • 著者名/発表者名
      K. Kushiro, A. Ryo, M. Takai
    • 学会等名
      EMN Biomaterials 2017 (Milan, Italy)
    • 国際学会 / 招待講演
  • [学会発表] K. Kushiro, A. Ryo, M. Takai2017

    • 著者名/発表者名
      Influences of Microtopography and Fluid Flow on Cancer Cell Migration
    • 学会等名
      IUMRS-ICAM 2017 (京都、京都大学)
    • 招待講演
  • [学会発表] 3Dプリンターで作製した三次元構造体の傾斜の角度と細胞移動の関係性2017

    • 著者名/発表者名
      柳沼友博、久代京一郎、笠間敏博、三宅亮、高井まどか
    • 学会等名
      Cheminas 35 (群馬県、桐生市市民文化会館)
  • [学会発表] Effects of Material Elasticity and Surface Adhesivity on Topography-Directed Cell Migration2017

    • 著者名/発表者名
      Keiichiro Kushiro, Tomohiro Yaginuma, Madoka Takai
    • 学会等名
      Cheminas 35 (東京、東京工業大学)

URL: 

公開日: 2018-12-17  

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