2022 Fiscal Year Final Research Report
Study of intestinal tumor based on the interaction of cellular diversity with tumor microenvironment
Project/Area Number |
20K07603
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
SAKAHARA Mizuho 公益財団法人がん研究会, がん研究所 細胞生物部, 博士研究員 (00572314)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 消化管腫瘍 / 細胞多様性 / 腫瘍微小環境 / 発がんモデルマウス |
Outline of Final Research Achievements |
Cell diversity and tumor microenvironment is considered to be the causes of treatment-resistant in colorectal cancer. To investigate the functional interaction of RAS mutation with cellular diversity, we performed single-cell RNA sequencing (scRNA-seq) analysis using genetically modified mice and their organoid. Through scRNA-seq analysis, we found that tumor cells with Kras mutation secreted humoral factor with or without alteration of cellular diversity. We focused on humoral factor which is reported to be associated with recruitment of immune cells in tumor microenvironment. Using pharmacological intervention, we found that humoral factor plays an important role in the interaction of tumor cells with immune cells in Apc/Kras intestinal tumor mice. These observations suggest that cellular diversity is induced by Kras mutation modulate the immune microenvironment in intestinal tumor.
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Free Research Field |
細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
大腸がんは様々な遺伝子変異の蓄積によって悪性化する。本研究では、「Kras変異による細胞多様性の変化」とそれに伴う腫瘍微小環境中の液性因子分泌量の変動、さらにその結果生じる免疫微小環境への影響を明らかにした。 腫瘍関連分子の研究は、それら分子の転写調節やシグナル伝達経路に着目したものが多い。本研究成果は、従来の「Rasシグナル活性化」による腫瘍細胞自身の形質転換に加え、「腫瘍組織の細胞多様性」および「腫瘍微小環境の免疫系変化」の機能的相関を示しており、RASによる免疫回避の新たな概念の提示と治療法開発につながることが期待される。
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