Analysis of stromal cell reprogramming induced by cancer stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02900
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: YAMASHITA TARO 金沢大学, 医学系, 教授 (90377432)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 癌幹細胞 / 遠隔転移 / 上皮間葉転換

Outline of Final Research Achievements

We previously demonstrated that two distinct cancer stem cells, namely EpCAM-positive epithelial cancer stem cells and CD90-positive mesenchymal cancer stem cells, exit in human hepatocellular carcinoma. Especially, CD90-positive cancer stem cells play a fundamental role on distant organ metastasis of hepatocellular carcinoma. Here we evaluated the role of cancer associated fibroblasts on EpCAM-positive epithelial cancer stem cells. We found that the presence of cancer associated fibroblasts activated the JUNB transcription factor to induce CD90-positive mesenchymal cancer stem cells, resulted in the acquisition of metastatic capacity of EpCAM-positive epithelial cancer stem cells. Thus, our study demonstrated the novel role of JUNB on epithelial-mesenchymal transition and cancer metastasis, suggested that JUNB might be a good molecular target to prevent HCC metastasis.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌の遠隔転移は患者の予後不良につながる一方、遠隔転移プログラムを阻害する治療薬はない。我々はCD90陽性癌幹細胞が遠隔転移を起こし、その血清マーカーとしてLG2mを同定したが、治療薬候補はまだ開発できていない。本研究では上皮系癌幹細胞から間葉系癌幹細胞が出現する機序として癌関連線維芽細胞の役割を同定、その機序として腫瘍辺縁部におけるJUNBの活性化を見出し、JUNB過剰発現が遠隔転移を起こすことを同定した。本研究成果から、JUNBを標的にした薬物候補の開発が肝細胞癌の遠隔転移阻害剤として有望な可能性が示唆され、新たな癌分子標的の創出に至ったと考える。