| Project/Area Number |
22K15532
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Adipsin / Adipocyte / Breast cancer / Cancer stem cell |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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