Analysis of factors associated with the development of gastric cancer in hypoxic microenvironment

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390329
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka City University
• Principal Investigator: YASHIRO Masakazu 大阪市立大学, 医学(系)研究科(研究院), 准教授 (60305638)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 癌周囲低酸素環境 / 胃癌 / スキルス胃癌細胞 / 癌関連線維芽細胞 / CXCL12 / CXCR4 / 分子標的治療

Outline of Final Research Achievements

This study investigated the growth-signaling of gastric cancer (GC) cells in focus on the interaction with cancer-associated fibroblasts (CAFs) and gastric cancer (GC) cells under normoxia and hypoxia. Nine cell lines, including four diffuse-type GC cell lines, two intestinal-type GC cell lines, and three CAF cell lines were used. Cells were examined for expression CXCR4, FGFR2 and SDF1. CXCR4 expression by diffuse-type GC cells was significantly increased in hypoxia, while FGFR2 expression was decreased. FGFR2 inhibition significantly decreased the activity of CAFs for diffuse-type GC cells in normoxia but not in hypoxia. In contrast, CXCR4 inhibition significantly decreased the activity of CAFs in hypoxia. HIF1 siRNA significantly decreased both CXCR4 expression by diffuse-type GC cells and SDF1 production by CAFs. These findings suggest that diffuse-type GC cells might switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis through HIF1 in hypoxic microenvironments.

Free Research Field

医歯薬学