The kinetics and modulation of tumor-initiating cells regulated by cell differentiation and dedifferentiation in de novo primary liver cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: Ohtsuka Masayuki 千葉大学, 医学(系)研究科(研究院), 講師 (90334185)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI MASARU 千葉大学, 大学院医学研究院, 教授 (70166156) ; SHIMIZU HIROAKI 千葉大学, 大学院医学研究院, 准教授 (80272318) ; YOSHITOMI HIDEYUKI 千葉大学, 医学部附属病院, 講師 (60375631) ; OKAMURA DAIKI 千葉大学, 大学院医学研究院, 特任講師 (50375698) ; NAKAJIMA MASAYUKI 千葉大学, 医学部附属病院, 助教 (80466705)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 癌源細胞 / 肝内胆管癌 / 肝細胞癌 / 分化・脱分化 / de novo癌

Outline of Final Research Achievements

In intrahepatic cholangiocarcinomas, gankyrin was highly expressed, which correlated with Oct4 and OV6 expressions. Patients with ICC expressing high levels of gankyrin, Oct4 or OV6 had significantly poor prognosis following surgical resection. Although no marked effects of gankyrin overexpression was observed, knockdown of gankyrin was associated with the decreases of Oct-4 expression and OV-6 positive cell population in vitro. Furthermore, gankyrin knockdown deteriorated sphere-forming ability. These results suggested that Gankyrin might play an important role in the maintenance of cancer cells with stem-like features that could act as tumor-initiating cells induced by cell dedifferetriation in intrahepatic cholangiocarcinoma. MicroRNA-214 regulated gankyrin expression, and transfection of microRNA214 was found to induce cell differentiation in hepatocellular carcinoma cells through downregulation of gankyrin expression.

Free Research Field

医歯薬系　外科系臨床医学・消化器外科学