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2021 Fiscal Year Final Research Report

Investigation of tumor suppression mechanism by TME reprogramming using pancreatic organoids

Research Project

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Project/Area Number 20K16361
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKyushu University

Principal Investigator

CHIJIIWA Yoshiro  九州大学, 医学研究院, 共同研究員 (60783701)

Project Period (FY) 2020-04-01 – 2022-03-31
Keywords膵癌 / 腫瘍微小環境 / 膵星細胞 / オルガノイド
Outline of Final Research Achievements

By comparing pancreatic stellate cells (PSCs) derived from patients with pancreatic cancer and chronic pancreatitis, we were able to demonstrate at the in vitro / vivo level that suppressing ERAP2, which was upregulated in cancer-derived PSCs, can convert tumor-promoting PSCs to a quiescent state, resulting in suppressing tumor growth and fibrosis levels.
Furthermore, the effects of the tumor microenvironment (TME) on pancreatic organoids (PDOs) were examined, and it was shown that the PDO phenotype is maintained by niche factors secreted by cancer-associated fibroblasts (CAFs), and that well differentiated PDOs were also shown to upregulate the expression of mevalonic acid pathway-related genes in correlation with niche dependence.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、PSCのERAP2は小胞体由来のオートファジーを介してPSCの活性化も制御し、ひいては腫瘍増大と線維化レベルを抑制していることが示唆された。以上からは、ERAP2が膵癌治療に対する有望な治療標的となり得るといえる。
加えてPDOを用いた検討では、TMEにおけるCAF由来のニッチ因子がPDOの分化型を維持しており、高分化型PDOはニッチ依存性と相関してアップレギュレートされる経路があることが示された。このことは、新たな膵癌サブタイプ分類ベースの治療戦略の開発の必要性を訴える結果といえる。

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Published: 2023-01-30  

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