Development of novel therapeutics against ion transporters expressed in cancer-associated fibroblast

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16518
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shimizu Hiroki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00756827)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 癌関連線維芽細胞 / 大腸癌 / 膜輸送体

Outline of Final Research Achievements

Primary cultured cancer associated fibroblast and normal fibroblast obtained from surgical resected specimen of colon cancer patients were used for mRNA micoarray analysis and revealed that the expression of L-type amino acid transporter 1（LAT1(SLC7A5)）was significantly higher in cancer associated fibroblast than normal fibroblast. Although further experiments were planed using siRNA transfection technique, primary cultured fibroblasts got weak due to cell senescence and we could not proceed in-vitro experiments. In order to overcome this problem, we visited other institutes where experiments using primary cultured fibroblasts had been performed and we improved our protocols. We also learned about immortalization of primary cultured fibroblasts and started using these immortalized cells to proceed in-vitro experiments. IHC for LAT1 using colon cancer tissues was also planed to clarify the association between LAT1 expression and clinicopathological features of colon cancer patients.

Free Research Field

functions of transporters and channels in cancer

Academic Significance and Societal Importance of the Research Achievements

今回、正常組織より癌組織癌の線維芽細胞においてLAT1が高発現であることを見いだしたが、これがヒト臨床サンプルが元になっていることにまず意義がある。LAT1は大腸癌を含め種々の癌組織で高発現を認め、癌進展に関与していることが報告されているうえ、LAT1阻害剤の開発も進められており癌治療の有望な標的分子である。癌関連線維芽細胞におけるLAT1の意義についてはこれまで報告がないため、それが判明すれば癌治療に応用できる可能性を秘めている。また、細胞実験だけでなく大腸癌切除標本を用いた免疫染色法でも同時に検討を始めており、臨床データを使用できるため実臨床に則した研究であることに意義がある。