Analysis of the interaction between myeloid derived cells and esophageal squamous cell carcinoma cells in the humanized mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07373
• 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: Yokozaki Hiroshi 神戸大学, 医学研究科, 教授 (10200891)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ヒト化マウス / 骨髄由来細胞 / 食道扁平上皮癌 / 細胞間相互作用 / 癌微小環境

Outline of Final Research Achievements

A human esophageal squamous cell carcinoma (ESCC) cell line TE-11 was subcutaneously transplanted in humanized mice to elucidate the roles of tumor associated macrophages (TAMs) in the progression of ESCC in vivo. Growth of the transplanted tumor was significantly promoted than that of negative controls after 50 days. Immunohistochemical analysis demonstrated that significant number of human CD163+ TAMs infiltrated in the transplanted tumor, indicating their bone marrow/peripheral blood monocyte origin. In addition, CD34+ micro-vessel density was higher in the transplanted tumor in humanized mice than non-humanized mice. This research project proved that cancer cell transplantation in humanized mice may provide a satisfactory model for the analysis of the human ESCC tumor microenvironment including TAMs and other stromal cells in vivo.

Free Research Field

腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

ヒト造血幹細胞を移植した高度免疫不全マウス体内で機能的なヒト型血液、免疫細胞が出現する状態を狭義の「ヒト化マウス」と呼ぶ。ヒト化マウスのがん研究への応用は、これまで白血病、リンパ腫等造血器腫瘍の発生機構探索が主体であり、固形癌移植に関しては治療開発のヒト化モデルとして使用されることが殆どであった。ヒト化マウス移植食道扁平上皮癌細胞とヒト型造血・免疫系細胞の間にもたらされる、生体内での癌細胞－TAM相互作用の実態を形態・分子の両面から可視化することにより、癌細胞－TAM相互作用を標的とした食道扁平上皮癌制御戦略の創造が期待される。