Functional elucidation of S100A10 in the acquisition of invasive and metastatic abilities of cholangiocarcinoma and its development into therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08795
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shinshu University
• Principal Investigator: Kojima Katsuhiko 信州大学, 学術研究院医学系, 講師 (80345743)
• Co-Investigator(Kenkyū-buntansha): 竹下 敏一 信州大学, 学術研究院医学系, 教授 (60212023)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: S100A10 / 胆管癌 / 転移 / 腫瘍微小環境

Outline of Final Research Achievements

One of the factors leading to the decreased cell motility caused by the knockout of S100A10, which is expressed in cholangiocarcinoma cells, is the observed reduction in the expression of vimentin, an epithelial-mesenchymal transition (EMT) marker. However, no changes were observed in the expression of other EMT markers, suggesting that S100A10 plays a mechanical role in the intracellular dynamics of vimentin and the actin cytoskeleton. The introduction of low molecular weight inhibitors against S100A10 or VHH antibodies obtained through screening into the cells reproduced the decreased cell motility and actin cytoskeleton abnormalities similar to the knockout experiments, and dysfunction due to vimentin aggregation was observed.

Free Research Field

機能生物化学

Academic Significance and Societal Importance of the Research Achievements

最も治療抵抗性、予後不良を示す癌腫である胆管癌の悪性形質のひとつである「浸潤転移」に関する解析は乳癌や大腸癌と比較して不十分であった。本研究は、S100A10が細胞遊走につながる細胞骨格の細胞内動態を機械的に制御する重要な分子であることを明らかにした点で学術的意義を持つ。また、スクリーニングから得た抗S100A10-VHH抗体の胆管癌由来細胞内における発現が、細胞骨格異常を誘導し細胞遊走能を低下させることを見出した。この結果は、胆管癌の浸潤転移を抑制する分子標的薬につながるものと期待できる点で社会的意義を持つと考えている。