Mechanisms for the stromal construction of the scirrhous gastric cancer: role of myeloid cells and cancer stem cells on the formation of tumor stroma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02883
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka City University
• Principal Investigator: Yashiro Masakazu 大阪市立大学, 大学院医学研究科, 准教授 (60305638)
• Co-Investigator(Kenkyū-buntansha): 中前 博久 大阪市立大学, 大学院医学研究科, 准教授 (30364003)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: スキルス胃癌 / CXCL1 / CXCR2 / 線維芽細胞 / 骨髄由来細胞

Outline of Final Research Achievements

Tumor stromal cells play a critical role in the progression of scirrhous gastric cancer (SGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. The influences of CXCR2 inhibitor on the migration of bone marrow-derived mesenchymal cells (BM-MCs) were examined both in vitro and in vivo. BM-MCs frequently migrated into stroma of DGC in vivo. CXCL1 from DGC cells stimulated the chemoattractant ability of BM-MCs. CXCR2 inhibitor decreased the migration of BM-MCs, stimulated by SGC cells. A CXCR2 inhibitor reduced the recruitment of BM-MCs into the tumor in vivo, decreasing tumor size and lymph node metastasis, and prolonging the survival of gastric tumor-bearing mice. These findings suggested that CXCL1 from SGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs. Inhibition of BM-MC recruitment via the CXCL1-CXCR2 axis appears a promising therapy for SGC.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

スキルス胃癌細胞の産生するCXCL1が間葉系幹細胞のCXCR2に作用してCAF増生を招来するメカニズムを世界に先駆けて明らかにした。この成果に基づき、CXCR2阻害あるいはスキルス胃癌細胞産生のCXCL1を阻害してCAF増生を抑制するスキルス胃癌治療法が開発されれば、比較的若年に発症する難治癌であるスキルス胃癌の予後が改善されるため、社会的意義が大きい。