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Suppression of metastasis of bone and soft tissue sarcoma by regulation of cell movement polarity via cytoskeleton

Research Project

Project/Area Number 20K16353
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionUniversity of Toyama

Principal Investigator

Watanabe Kenta  富山大学, 附属病院, 診療助手 (90865255)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords細胞骨格 / 細胞運動極性 / 転移抑制 / 細胞骨格転 / 肺転移 / 肉腫 / 細胞運動 / 細胞極性
Outline of Research at the Start

肺転移を有する骨軟部肉腫患者の5年生存率は、いまだ約20%と予後不良な疾患であり、転移抑制が課題である。この課題を克服するため、多段階過程からなる転移形成に関与する肉腫細胞の運動能に重要な役割を担う細胞骨格を調整することによって、肉腫の新規転移抑制が可能であることを検証する。

Outline of Final Research Achievements

The purpose of this study was to create a new method for inhibiting metastasis by focusing on the relationship between metastatic potential and cytoskeleton using metastatic strains with different metastatic potentials established from mouse bone and soft tissue sarcoma cells. As for the research method, we focused on the polarity of cell movement, especially in the cytoskeleton, and planned to analyze the regulation mechanism of cell movement by microtubule plus-end-accumulating proteins.
In 2D and 3D cultures, it was confirmed that eribulin, a microtubule inhibitor, reduced the directivity of cell motility, and that the principle of this was a change in the localization of APC. Next, we focused on microtubule + end-accumulating proteins such as APC, and created knockout strains and overexpressed strains, but could not establish stable cell lines.

Academic Significance and Societal Importance of the Research Achievements

目的の新たな転移抑制の治療法の確立には至らなかったが、細胞運動極性の調整が転移の抑制につながる可能性は考えられた。今後安定した遺伝子操作による細胞株の樹立により、より詳細に細胞運動極性の機序、調整をすることが可能となれば現在治療困難である骨軟部肉腫の転移の抑制につながる治療法の確立を目指すことができるのではないかと考える。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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