Identification and functional analysis of a liver stromal cell-derived factor contributing to liver metastasis of colorectal cancer cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08693
• 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: Microbial Chemistry Research Foundation
• Principal Investigator: Tomokazu Ohishi 公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 主任研究員 (50442546)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: がんー間質相互作用

Outline of Final Research Achievements

In this study, we tried to identify a novel molecule, which is involved in the liver metastasis of colorectal cancer. We sought the possibility of a new therapeutic strategy targeting the molecule for the treatment of liver metastasis of colorectal cancer. 1)Plasminogen activator inhibitor-1 (PAI-1), a negative regulator of the fibrinolytic pathway is identified as a candidate of promoting factor of liver metastasis of colorectal cancer. 2) Treatment of PAI-1 inhibitor suppressed liver metastasis of colorectal cancer in a mouse model of liver metastasis of colorectal cancer. 3)Similarly, PAI-1 knockout mice suppressed liver metastasis of colorectal cancer compared with wild-type mice.
Taken together, PAI-1 promotes liver metastasis of colorectal cancer and inhibition of PAI-1 may suppress liver metastasis of colorectal cancer.

Free Research Field

基礎医学

Academic Significance and Societal Importance of the Research Achievements

大腸がんは国内罹患数が最も高いがんであり、早急な対応が急務である。大腸がんの転移は患者の予後不良に直結し、約7~8割を占める大腸がん肝転移の制御が重要である。現在、抗上皮成長因子受容体（EGFR）抗体薬が推奨されていないRAS変異型の大腸がん患者の存在が問題となっており、新たな治療戦略が求められてきた。我々が見出したPAI-1は大腸がん肝転移を促進する因子であることから、新たな治療標的として考えられる。その阻害剤や中和抗体は、抗EGFR抗体薬不応性のがんにも適用できると見込まれ、社会的意義は大きい。