Research for the trial of cancer cell removal from fibrotic tissues by disturbing mechanosensitizer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Akita University
• Principal Investigator: Kuriyama Sei 秋田大学, 医学系研究科, 准教授 (30398226)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: メカノセンシング / FRET / がん浸潤・転移

Outline of Final Research Achievements

Tumors tend to grow preferentially on stiff substrates in tissue. It is known that fibrosis increases organ stiffness due to the production of abnormal extracellular matrices by the tumor microenvironment. However, the precise way in which cancer cells sense the stiffness of their surroundings is less understood. Therefore, we aimed to measure cell surface tension, which is generated by the actin cytoskeleton, using a molecular biosensor. In this study, we compared measurements taken from a mechano-gel with a known Young’s modulus to those taken from sections of lung tumor nodules. The tension biosensor is based on Forster Resonance Energy Transfer (FRET) technology, which estimates distances between two fluorophores based on the amount of energy transferred. We developed a method to measure FRET efficiency in both gel and tissue samples without quenching the fluorescence.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がんによる死亡原因の大半はがん転移によって引き起こされる多臓器不全である。がん免疫が患者に光明をもたらしているが、転移を予測、診断する方法の開発は社会的な急務である。今回は組織の硬さを測定するのではなく、がんが感じている硬さを知ろうとする研究である。がん細胞は何らかの変異を抱えていて正常細胞とは多くの点で異なっている。がん細胞が感知していた腫瘍周辺のかたさは約20kPaと平滑筋に近く、正常な肺が0.2kPaである事を考えると随分と異なっていた。他の技術を用いて答え合わせも必要であるがこのズレに注目して様々ながんの悪性度とズレの大きさを調べていく必要があるのではないかと考えている。