Establishment of human cancer microenvironment mouse model

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kumamoto University
• Principal Investigator: OKADA SEIJI 熊本大学, エイズ学研究センター, 教授 (50282455)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 患者由来腫瘍移植モデル / 高度免疫不全マウス / 胆管細胞癌 / 悪性リンパ腫 / 固形癌 / がん微小環境

Outline of Final Research Achievements

We established cholangiocarcinoma lung and liver metastasis model, and showed that CD147 played important role for epithelial-mesenchymal transition and metastasis. We also established patient-derived xenograft (PDX) model of liver fluke derived cholangiocarcinoma. Five cell lines were established from 12 PDX samples.
We showed that autophagy is accelerated in Primary effusion lymphoma (PEL) and inhibition of autophagy induced apoptosis for PEL cells. We also showed that transcriptional factor, PU.1, is methylated in PEL cells and activation of PU.1 induced apoptosis for PEL cells. These results indicate that epigenetic regulation can be important target for treatment of PEL.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

高度免疫不全マウスへの移植系を用いて難治性腫瘍であるヒト胆管細胞癌と悪性リンパ腫にヒト由来腫瘍細胞を移植する事でマウス生体内に「ヒトのがん微小環境」を構築した。本系は、ヒト腫瘍のAvatarとして難治性腫瘍の病態解析と治療薬開発に有用な系として期待される。また、悪性リンパ腫のエピジェネチックな制御機構の一端を解明し、新規治療法開発の可能性を示唆した。