Mechanism of suppressive effect for intrahepatic recurrence of hepatocellular carcinoma by hepatic stellate cell regulation after liver transplantation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: IMURA Satoru 徳島大学, 病院, 特任教授 (90380021)
• Co-Investigator(Kenkyū-buntansha): 常山 幸一 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10293341) ; 池本 哲也 徳島大学, 病院, 特任教授 (20398019) ; 岩橋 衆一 徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (30531751) ; 齋藤 裕 徳島大学, 病院, 特任助教 (50548675) ; 森根 裕二 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝細胞癌 / 腫瘍微小環境 / 肝星細胞 / 肝移植 / 再発

Outline of Final Research Achievements

We studied the mechanism of hepatocellular carcinoma (HCC) progression focused on hepatic stellate cells (HSC) in cancer microenvironment. In HCC, (1) HSC have roles such as increasing the malignancy of cancer cells and promoting metastasis. (2) HSC is induced into cancer-related fibroblasts (CAF) by HCC cells, by secreting IL-6 and activating the IL-6-Stat3 pathway, it acts on EMT induction, cancer growth, and stemness acquisition. (3) CAF converts M0 macrophages (MΦ) to M2 MΦ (tumor-related MΦ: TAM), and TAM-derived VEGF induces EMT in cancer cells, thereby forming a cancer cell-CAF-TAM interaction in the tumor microenvironment.

Free Research Field

医歯薬学・外科系臨床医学・消化器外科学

Academic Significance and Societal Importance of the Research Achievements

肝癌の進展・転移の課程で、腫瘍微小環境における肝星細胞の役割、肝星細胞制御による進展・転移を抑制することができれば肝癌治療の成績向上が期待できる。肝癌の腫瘍微小環境における癌細胞-癌関連線維芽細胞-腫瘍関連マクロファージの相互作用を明らかにしたことは、転移を伴う肝癌治療を困難にしてきた問題を克服する可能性がある肝星細胞研究の意義は高い。