• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2017 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number 16H05972
Research InstitutionThe University of Tokyo

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)

Project Period (FY) 2016-04-01 – 2020-03-31
KeywordsCell Migration / Cancer / Microtopography / Mechanotransduction / EMT
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.

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.

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.

  • Research Products

    (11 results)

All 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

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

    • Author(s)
      Carlton F. O. Hoy, Keiichiro Kushiro, Madoka Takai
    • Journal Title

      Analyst

      Volume: 143 Pages: 865-873

    • DOI

      10.1039/C8AN90024H

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences in Three-Dimensional Geometric Recognition by Non-Cancerous and Cancerous Epithelial Cells on Microgroove-Based Topography2017

    • Author(s)
      Kushiro K, Yaginuma T, Ryo A, Takai M
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 4244

    • DOI

      10.1038/s41598-017-03779-6

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influence of Fluid Flow on Microtopography-Guided Cell Migration and Underlying Mechanotransduction2017

    • Author(s)
      K. Kushiro, A. Ryo, M. Takai
    • Journal Title

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

      Volume: 1 Pages: 830-831

  • [Journal Article] Single Cell Resolution Analysis of Ultrasound-Produced Multi-Cellular Tumor Spheroids2017

    • Author(s)
      K. Olofsson, V. Carannante, T. Frisk, K. Kushiro, M. Takai, A. Lunduist, B. Onfelt, M. Wiklund
    • Journal Title

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

      Volume: 1 Pages: 955-956

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

    • Author(s)
      K. Kushiro, A. Ryo, M. Takai
    • Organizer
      MicroTAS 2017 (Savannah, Georgia, USA)
    • Int'l Joint Research
  • [Presentation] Single Cell Resolution Analysis of Ultrasound-Produced Multi-Cellular Tumor Spheroids2017

    • Author(s)
      K. Olofsson, V. Carannante, T. Frisk, K. Kushiro, M. Takai, A. Lunduist, B. Onfelt, M. Wiklund
    • Organizer
      MicroTAS 2017 (Savannah, Georgia, USA)
    • Int'l Joint Research
  • [Presentation] TOPOGRAPHICAL SYSTEMS FOR SINGLE-CELL MIGRATION ANALYSIS TO DISTINGUISH NORMAL AND CANCEROUS CELL TYPES2017

    • Author(s)
      K. Kushiro, A. Ryo, M. Takai
    • Organizer
      AIBBC 2017 (Nairobi, Kenya)
    • Int'l Joint Research / Invited
  • [Presentation] Effect of Biomaterial Surface Structures and Material Properties on Topography-Driven Cell Migration2017

    • Author(s)
      K. Kushiro, A. Ryo, M. Takai
    • Organizer
      EMN Biomaterials 2017 (Milan, Italy)
    • Int'l Joint Research / Invited
  • [Presentation] K. Kushiro, A. Ryo, M. Takai2017

    • Author(s)
      Influences of Microtopography and Fluid Flow on Cancer Cell Migration
    • Organizer
      IUMRS-ICAM 2017 (京都、京都大学)
    • Invited
  • [Presentation] 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

    • Author(s)
      柳沼友博、久代京一郎、笠間敏博、三宅亮、高井まどか
    • Organizer
      Cheminas 35 (群馬県、桐生市市民文化会館)
  • [Presentation] Effects of Material Elasticity and Surface Adhesivity on Topography-Directed Cell Migration2017

    • Author(s)
      Keiichiro Kushiro, Tomohiro Yaginuma, Madoka Takai
    • Organizer
      Cheminas 35 (東京、東京工業大学)

URL: 

Published: 2018-12-17  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi