Mouse mammary carcinoma cell lines release microvesicles containing precurcer VEGF-C

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka Medical College
• Principal Investigator: Ito Yuko 大阪医科大学, 医学部, 准教授 (40148432)
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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

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.

Free Research Field

医学