Investigation of peritoneal dissemination mechanism through trans-vessel route in scirrhous gastric cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Saga University
• Principal Investigator: Ikeda Osamu 佐賀大学, 医学部, 客員研究員 (70523124)
• Co-Investigator(Kenkyū-buntansha): KITAJIMA Yoshihiko 佐賀大学, 医学部, 研究員 (30234256)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Jun 佐賀大学, 医学部, 助教 (60404175)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: スキルス胃癌 / 低酸素環境 / HIF-1α / ANGPTL4 / アノイキス / 細胞周期

Outline of Final Research Achievements

We isolated ANGPTL4 gene as a HIF-1α target in scirrhous gastric cancer (SGC). ANGPTL4 expression was investigated in 9 GC cells under normoxia and hypoxia (1%O2). ANGPTL4 was specifically expressed in SGC cells with the hypoxic induction. Thus present study focused on investigating the biological function of ANGPTL4 in scirrhous gastric cancer (SGC) cells. Stable ANGPTL4 knockdown (KD) and control (SC) cells were established in SGC cells, 58As9. In monolayer culture, cell proliferation was decreased in KD. FACS analysis showed hypoxia-induced cell cycle arrest at G1. In suspension culture, strong apoptosis (anoikis) was induced in hypoxic KD. In vivo analysis showed that KD cells lost the tumorigenicity in nude mice. Analysis of intracellular signaling further revealed that TGF-β pathway was activated in KD, whereas FAK/Src/AKT activity was decreased. ANGPTL4 may increase cancer aggressiveness via TGF-β and signal and FAK/Src/AKT signal in hypoxic SGC cells.

Free Research Field

胃癌の分子生物学