Search for new diagnostic and therapeutic targets in esophageal intraepithelial neoplasia: the role of interaction between macrophages and esophageal squamous epithelial cells in carcinogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology; Experimental pathology
• Research Institution: Kobe University
• Principal Investigator: Koma Yuichiro 神戸大学, 医学研究科, 講師 (40714647)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 食道扁平上皮癌 / 食道上皮内腫瘍 / マクロファージ / 癌・間質相互作用 / 発癌初期段階

Outline of Final Research Achievements

We observed that infiltrating macrophages (Mφs) were upregulated in esophageal precancerous lesions. Based on these findings, we established a coculture assay using human esophageal epithelial cells (Het-1A) and human acute monocytic leukemia cells (THP-1)-derived Mφs to study the roles of Mφs in esophageal carcinogenesis. In this study, we performed cDNA microarray analysis between monocultured Het-1A and co-cultured Het-1A with THP-1-derived Mφs, and found that CSF3/G-CSF expression was upregulated in Het-1A under co-culture conditions. Het-1A was found to express G-CSF receptors. Recombinant human CSF3/G-CSF (rhCSF3/G-CSF) induced cell migration and modulated GSK-3α/β-β-catenin signaling in Het-1A. Moreover, phospho-β-catenin (Ser675) expression levels were increased, and translocation of this protein from the cytoplasm to the nucleus was induced by rhCSF3/G-CSF. These results indicate that CSF3/G-CSF signaling may contribute to early esophageal carcinogenesis.

Free Research Field

人体病理学