Analysis of macrophages and cancer-associated fibroblasts in early stage of esophageal squamous carcinogenesis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kobe University
• Principal Investigator: Koma Yuichiro 神戸大学, 医学研究科, 准教授 (40714647)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 食道扁平上皮癌 / 癌・間質相互作用 / 癌関連線維芽細胞

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs) contribute to the progression of esophageal squamous cell carcinoma (ESCC). In this study, we established an indirect co-culture assay between human esophageal squamous epithelial cell line (Het-1A) and human mesenchymal stem cells (MSCs), one of the origins of CAFs, to understand the roles of CAFs in early stage of ESCC. Co-cultured MSCs showed increased expressions of the CAFs markers, and promoted cell growth and migration, when compared to monocultured MSCs. Then, we performed cDNA microarray and cytokine array analyses between monocultured and co-cultured MSCs, and found the higher expression and secretion of CCL2 in co-cultured MSCs. The recombinant human CCL2 protein promoted cell growth and migration in both MSCs and Het-1A. These results indicate that CCL2 may contribute to cell-to-cell interaction between CAFs and epithelial cells in early stage of ESCC.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

食道扁平上皮癌は難治癌の一つであり、早期の段階で診断・治療することが重要である。本研究では食道扁平上皮癌の発癌初期段階において癌関連線維芽細胞由来のケモカインCCL2が受容体CCR2を介して扁平上皮細胞と癌関連線維芽細胞の増殖・運動能を亢進させる可能性を見出した。CCL2-CCR2経路は食道扁平上皮癌の早期の段階での診断マーカーとしてだけでなく、新規治療標的分子としての発展が期待される。