| Project/Area Number |
17K09944
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
国崎 祐哉 九州大学, 大学病院, 講師 (80737099)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨髄造血微小環境 / 骨芽細胞 / 血管新生 / 白血病幹細胞ニッチ |
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| Outline of Final Research Achievements |
Previous studies have reported that leukemia stem cells are protected by vascular niche in the bone marrow. However, the regulatory mechanism for the vascular niche is still unknown. We focused on angiogenic factors from osteoblasts closely resided near vascular niche, and Fibroblast growth factor 2 (FGF2), which was prognostically significant for hematological malignancies. We found that osteoblasts secreted VWGF-A 165: the most potent isoform, and FGF2 induce VEGF-A secretion from osteoblasts with increased mRNA expression. Next, we examined whether FGF2 regulates the VEGF-A promoter activity. However, luciferase assays with mouse VEGF-A promoter showed FGF2 did not increase luciferase activity. These observations provide evidence that FGF2 does not regulate VEGF-A transcription in osteoblasts. Thus, we supposed that FGF2 up-regulated VEGF-A expression by accelerating VEGF-A mRNA stability or micro RNA.
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| Academic Significance and Societal Importance of the Research Achievements |
白血病幹細胞は、骨髄血管ニッチにより保護されているため、化学療法などに抵抗性となり再発につながる。しかし血管ニッチの制御機構は未だ不明である。我々は、血管ニッチ近傍に存在する骨芽細胞に注目し、血液悪性腫瘍予後不良因子であるFGF2の影響を検討した。骨芽細胞は、強力な血管新生因子であるVEGF-A165isoformを大量に分泌していた。したがって今後の検討により骨芽細胞由来VEGF-Aの血管ニッチにおける意義を確認すれば、新たな抗白血病幹細胞治療に結びつく可能性がある。
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