Significance of connective tissue growth factor (CTGF) and tumor-stroma interaction in Kras-driven hepatocarcinogenesis and HCC progression

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670381
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Takehara Tetsuo 大阪大学, 医学(系)研究科(研究院), 教授 (70335355)
• Co-Investigator(Kenkyū-buntansha): Hikita Hayato 大阪大学, 大学院医学系研究科, 助教 (20623044)
• Co-Investigator(Renkei-kenkyūsha): Makino Yuki 大阪大学, 大学院医学系研究科, 医員 (60771334)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Kras / CTGF / 発癌

Outline of Final Research Achievements

Connective tissue growth factor (CTGF) was found to be up-regulated in tumor area in a Kras-mutated HCC mouse model by the activation of Ras/Mek/Erk pathway. Hepatocyte-specific knockout of CTGF in this mouse model revealed significant decrease of tumor diameter, number, and liver/body weight ratio and better tumor differentiation degrees. In surgically resected human HCC, CTGF was up-regulated in tumor area in the same way as Kras-mutated HCC mouse model and CTGF expression levels were shown to be associated with the malignant grade of HCC. Although forced expression of CTGF in HCC cell lines did not affect the in vitro cell viability or tumor volume of xenograft models, they significantly increased in CTGF-overexpressing HCC cell lines in the coexistence of hepatic stellate cells. From these results, CTGF was proven to be the molecule that promotes HCC progression via tumor-stroma interaction between HCC cells and hepatic stellate cells.

Free Research Field

肝臓病学