| Project/Area Number |
25462003
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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 |
General surgery
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| Research Institution | Osaka Medical College |
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Principal Investigator |
Ito Yuko 大阪医科大学, 医学部, 准教授 (40148432)
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| Co-Investigator(Kenkyū-buntansha) |
Shibata Masa-aki 大阪保健医療大学, 保健医療学部, 教授 (10319543)
OTSUKI Yoshinori 大阪医科大学, 医学部, 教授 (50140166)
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| Co-Investigator(Renkei-kenkyūsha) |
AKAO Yukihiro 岐阜大学, 連合創薬医療情報研究科, 教授 (00222505)
NABIL Eid 大阪医科大学, 医学部, 講師 (50570165)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | microvesicle / exosome / VEGF-C / マウス乳癌細胞 / リンパ行性転移 / リンパ管新生 / オートクライン / microvesicles / 乳癌 / 乳癌のリンパ行性転移 / 転移性の差異 / microRNA / 低酸素 / exosomes / 乳癌細胞 / リンパ管形成 / matureVEGF-C / precursorVEGF-C / lymphangiogenesis / metastasis |
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| Outline of Final Research Achievements |
Using two mouse mammary carcinoma cell lines, Western blot analysis of VEGF-C demonstrated exosomal expression of premature VEGF-C (pre-VEGF-C) in both cell lines. To study target cells of that pre-VEGF-C, we used mouse endothelial cell line (UV2) which express VEGFR3. MVs in the cell lines enhanced cell proliferation and tube formation in MV-treated UV2 cells. To confirm VEGF-C/VEGFR3 interaction, Western blot and immunofluorescent analysis were performed for the MV-treated UV2 cells. After treated by MVs, UV2 strongly expressed phospho-Akt. Furthermore, neutrizing of VEGFR3 inhibited proliferation of UV2, whereas UV2 were treated by MVs. These results indicated that there was no significant difference of pre-VEGF-C between these MVs shed from low- and high-metastatic tumors, while both MVs enhanced lymphangiogenesis of endothelial cells. Highly metastatic BJMC3879 cell was suggested as another target cell of pre-VEGF-C packed in MVs, because this cell expressed VEGFR3.
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