| 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 2023)
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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 / Breast cancer / Adipokine / Invasion / Adipocyte / 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 investigated the role of mature adipocytes in breast tumor migration and invasion compared to adipocyte progenitor cells.
1.Mature adipocytes had a significantly higher capacity to induce breast tumor migration and invasion than adipocyte progenitor cells. Hepatocyte growth factor (HGF) restored the reduced invasion-promoting ability of Complement Factor D knockout (Cfd-KO) mature adipocytes.
2.In cancer cells co-cultured with mature adipocytes, invasion promoters galectin-7 (Lgals7) and matrix metalloproteinases (MMPs) were upregulated.
3.Utilizing a syngeneic mouse model, we observed that tumor growth and metastasis were significantly suppressed in Adipsin-KO mice, with reduced capsular formation, tumor invasion at the cancer-adipocyte interface, and distant metastasis.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We are feeding mice a high-fat diet to investigate the effect of Adipsin on regulating body weight. The first round of the experiment has been completed, and we are currently conducting the second round of in vivo experiments. However, the food intake amounts of the mice differ between the two experiments, causing some inconsistencies.
We are examining whether Adipsin-KO mice fed a high-fat diet can inhibit the growth of breast cancer tumors. Additionally, we are investigating whether high-fat diet-fed Adipsin-KO mice injected with breast cancer cells exhibit different immune cell infiltration in the tumor lesion.
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| Strategy for Future Research Activity |
We will address inconsistencies in mice's food intake during high-fat diet experiments by standardizing feeding protocols. Future work includes expanding our study to additional cohorts of Adipsin-KO and wild-type mice to investigate Adipsin's role in body weight regulation and breast cancer growth. We will also explore the molecular mechanisms underlying immune cell infiltration differences in tumor lesions of high-fat diet-fed Adipsin-KO mice.
Challenges such as variability in food intake and stress factors will be mitigated by controlling environmental conditions and maintaining consistent feeding schedules. We will employ rigorous randomization and blinding techniques to enhance the reliability of our results.
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