2021 Fiscal Year Final Research Report

Elucidation of the mechanism of cancer metastasis by circulating tumor cell clusters using proteomics for the exploration of novel therapeutic targets

Research Project

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Project/Area Number	19K16851
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	National Institutes of Biomedical Innovation, Health and Nutrition
Principal Investigator	Sato Yumi 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所プロテオームリサーチプロジェクト, 特任研究員 (10333353)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	がん転移 / 初代三次元培養 / プロテオミクス / スフェロイド
Outline of Final Research Achievements	Since distant metastasis is a cause of cancer mortality, it is crucial to clarify the mechanism of metastasis by circulating tumor cells (CTCs) and CTC aggregates (CTC-clusters). CTC-clusters have higher metastatic potential than single CTCs, and therefore we adopted the Cancer Tissue-Originated Spheroids (CTOS), which are prepared from tumor tissue and retain the similar characteristics to CTC-clusters as a research model for metastasis. Based on the phosphoproteomic analysis, we predicted kinase activities and phosphorylation signals that fluctuate during the adhesion process of cancer cell clusters and estimated candidate molecules involved in the adhesion process. Among the inhibitors for the predicted candidate molecules, we found inhibitors with adhesion-inhibitory and cytotoxic effects on suspension-cultured CTOSs.
Free Research Field	分子細胞生物学、腫瘍細胞学
Academic Significance and Societal Importance of the Research Achievements	がんの転移は予後不良につながるため、転移メカニズム解明による転移予防、転移巣への治療法開発はがん克服につながることが期待される。近年、従来研究に用いられていた樹立細胞株は体内の腫瘍組織の多くの性質を失っており、より腫瘍組織の性質を維持した三次元初代培養法が報告されるようになった。機器やサンプル調整法の改良により微量検体からの解析が可能となったプロテオミクス法を用い腫瘍組織由来三次元初代培養がん細胞塊の転移過程を解析することで、これまでの遺伝子発現解析とは異なる新たな関連分子、メカニズム解明につながる可能性があり、新規創薬標的の発見につながることが期待できる。