| 研究課題/領域番号 |
22K15532
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分50010:腫瘍生物学関連
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| 研究機関 | 藤田医科大学 |
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研究代表者 |
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2024年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | Adipsin / Adipocyte / Breast cancer / Cancer stem cell |
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| 研究開始時の研究の概要 |
Adipsin is mainly secreted from adipocytes and enhances the cancer stem cell (CSC) properties of breast cancer cells.
Adipsin secretion is dependent on adipocyte maturation.
Here, we investigate molecular mechanisms by which Adipsin regulates adipocyte maturation to promote adipocyte-CSC interactions.
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| 研究実績の概要 |
We isolated adipose-derived stem cells (ADSC) from the mammary fat pad of wild-type (WT) and Adipsin knockout (KO) mice and differentiated them into mature adipocytes.
1. Adipsin-KO inhibits the secretion of several cytokines and adipokines, including macrophage chemoattractant protein-1 (MCP-1) as determined by cytokine array analysis of cell culture medium from mature adipocytes.
2. Using a syngeneic mouse model of breast cancer, we discovered that the mammary fat pad tumors of Adipsin-KO mice are smaller than those of wild-type mice.
RT-qPCR analysis of mature Adipsin-KO and WT adipocytes revealed differential gene expression of multiple genes involved in fat droplet formation and biosynthesis.
3. Using a high-fat diet, we found that Adipsin-KO mice are resistant to diet-induced obesity.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have established the framework for investigating the role of Adipsin in adipocyte differentiation and the formation of fat droplets. We have identified the target genes that are differentially expressed during adipocyte differentiation between WT and Adipsin-KO adipocytes. We are currently attempting to identify the molecular mechanisms by which Adipsin interacts with target genes to form fat droplets.
Meanwhile, experiments on the role of Adipsin in the promotion of breast cancer are well-established, and we are currently investigating the molecular mechanism by which Adipsin inhibits tumor growth.
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| 今後の研究の推進方策 |
1. Using immunofluorescence staining and cell fractionation, followed by western blotting, we will determine the localization of Adipsin in adipocytes.
2. Using mass spectrometry, we will compare the proteome profiles of wild-type and Adipsin-deficient mature adipocytes.
3. We will investigate the molecular mechanisms through which Adipsin-KO inhibits obesity.
4. We will investigate whether Adipsin-KO fed a high-fat diet can inhibit the growth of breast cancer tumors.
5. Using wild-type, enzyme-activity-deficient, and signal-peptide-deficient Adipsin mutants, we will explore the autocrine regulatory pathways of Adipsin in adipocyte differentiation.
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