2023 Fiscal Year Research-status Report
Multiple functions of Adipsin in adipocyte-breast cancer cell interaction
| Project/Area Number |
22K15532
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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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| Keywords | Adipsin / Breast cancer / Adipokine / Invasion |
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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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| Causes of Carryover |
We were planning to conduct RNA sequencing analysis of breast tumor cell samples injected into obese wild-type and Adipsin-KO mice. RNA sequencing of approximately 10 samples is estimated to cost around 900,000 yen. However, due to issues with the high-fat diet regimen and inconsistent weight gain in Adipsin-KO mice, we could not prepare the tumor samples as scheduled. Therefore, we have postponed this experiment to 2024
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