Elucidation of regulatory mechanism of cancer microenvironment through stromal cell autophagy in hepatocellular carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka University
• Principal Investigator: Hikita Hayato 大阪大学, 大学院医学系研究科, 講師 (20623044)
• Co-Investigator(Kenkyū-buntansha): 阪森 亮太郎 大阪大学, 大学院医学系研究科, 特任講師 (10644685) ; 巽 智秀 大阪大学, 大学院医学系研究科, 准教授 (20397699)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝癌 / 肝癌微小環境 / 細胞間相互作用

Outline of Final Research Achievements

Hepatoma cells enhanced autophagy of hepatocytes stellate cells (HSCs). The enhanced autophagy of HSCs increased the expression of GDF15, which promoted the proliferation of hepatoma cells, indicating a mechanism of hepatocarcinoma progression through cell-cell interaction between hepatoma cells and HSCs via enhanced GDF15 secretion.

In hepatoma cells, STAT3 activation enhanced CTGF expression and secretion, and CTGF enhanced secretion of various IL-6 family molecules in HSCs, macrophages, sinusoidal endothelial cells, and T cells; IL-6 family molecules upregulated STAT3 expression and cell proliferation in hepatoma cells. We elucidated the existence of a mechanism of HCC progression by the microenvironment mediated by CTGF-IL-6 family molecules.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

肝癌微小環境による肝癌進展機序が明らかとなった。肝癌細胞だけでなく、間質細胞も肝癌の増殖に大きな影響を与えており、本研究課題の遂行で明らかとなった分子機序を治療標的とすることで、新たな肝癌治療の開発も期待される。本研究成果の社会的な意義は大きいと考える。