Role of HCV and periostin on the regulation of liver cancer stem cells

• Project/Area Number: 24590994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: ADACHI Masayuki 慶應義塾大学, 医学部, 助教 (70338028)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 癌幹細胞 / HCV / Periostin / 肝臓学

Outline of Final Research Achievements

The aims of the study are to investigate the role of HCV virus on the liver cancer stem cell (CSC) biology; and to investigate the role of periostin on the liver carcinogenesis. The novel findings of the manuscript include:　1) CD133+/SP subpopulation is a distinct CSC population in Huh7 cells; 2) transduction of HCV full-length replicon or HCV core protein expands CSC population and augments CSC properties through two different mechanisms including (a) HCV induced expansion of CSC population through potentiation of self-renewal capacity and (b) transition from non-CSC CD133-/SP cells to CSC CD133+/SP cells; 3) HCV-mediated expansion of CSC population and augmentation of CSC properties are mediated by HIF-1α stabilization; 4) periostin KO mice did not develop CCL4-induced liver fibrosis as compared with WT mice; and 5) periostin KO mice did not develop DEN-induced liver tumors.

Research Products

• [Presentation] Hepatitis C Virus Core Protein Enhnces the Cancer Stem Cell-like Properties in Hepatocellular Carcinoma Cell Line via Hypoxia Inducible Factors (HIFs) (2012)
  • Author(s): Masayuki Adachi, Hiromasa Takaishi, Toshifumi Hibi
  • Organizer: Annual Meeting of American Association Study of Liver Disease
  • Place of Presentation: アメリカ合衆国 ボストン