2013 Fiscal Year Final Research Report
ADAMTS1 metalloproteinase inhibits lymphangiogenesis and mechanobiology of lymphangiogenesis
Project/Area Number |
23612004
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Mechanobiology
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Research Institution | Okayama University |
Principal Investigator |
INAGAKI Junko 岡山大学, 医歯(薬)学総合研究科, 助教 (90271056)
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Co-Investigator(Kenkyū-buntansha) |
IROHATA Satoshi 岡山大学, 国際センター, 准教授 (90332791)
NINOMIYA Yoshihumi 岡山大学, 医歯薬学総合研究科, 教授 (70126241)
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Co-Investigator(Renkei-kenkyūsha) |
NARUSE Keiji 岡山大学, 医歯薬学総合研究科, 教授 (40252233)
|
Project Period (FY) |
2011 – 2013
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Keywords | ADAMTS1 / 細胞外マトリックス / がん内圧 / リンパ管新生 |
Research Abstract |
ADAMTS1 is a matrix metalloproteinase and inhibits angiogenesis. We investigated the effect of ADAMTS1 on lymphangiogenesis. We further examined the relationship between tumor interstitial fluid pressure (TIFP) and tumor growth. We demonstrated that overexpressed-ADAMTS1 transfectants bind to VEGFC and made a complex and dampened the phosphorylation of VEGFR3, inhibiting lymphangiogenesis. Moreover, when VEGFC was injected to enhance lymphangiogenesis in a xenograft mouse model, TIFP was reduced and tumor growth was also attenuated. Finally, we stretched HMVEC-dLys and examined lymphangiogenesis-related genes. Mechanical stress may be involved in the regulation of lymphangiogenesis-related gene expressions in lymphatic endothelial cells.
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[Journal Article] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor2014
Author(s)
Inagaki J., Takahashi K., Ogawa H., Asano K., Hatipoglu O.F., Zeynel Cilek M., Obika M., Ohtsuki T., Hofmann M., Kusachi S., Ninomiya Y., Hirohata S.
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Journal Title
Exp. Cell Res
Volume: 323(2)
Pages: 263-75
DOI
Peer Reviewed
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[Journal Article] The tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis2012
Author(s)
Obika M., Ogawa H., Takahashi K., Li J., Hatipoglu O.F., Cilek M.Z., Miyoshi T., Inagaki J., Ohtsuki T., Kusachi S., Ninomiya Y., Hirohata S.
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Journal Title
Cancer Sci. 2012
Volume: 103(10)
Pages: 1889-1897
DOI
Peer Reviewed
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[Journal Article] a novel acute hypoxia-response sequence, drives reporter gene under hypoxia in vitro and in vivo2011
Author(s)
Cilek M.Z., Hirohata S., Hatipoglu O.F., Ogawa H., Miyoshi T., Inagaki J., Ohtsuki T., Harada H., Kamikawa S., Kusachi S., Ninomiya Y.
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Journal Title
Cell Biol Int. 2011
Volume: 35
Pages: 1-8
DOI
Peer Reviewed
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[Presentation] ADAMTS1プロモーターを利用した低酸素感受性発現ベクター2012
Author(s)
Hirohata S., Asano K., Cilek M.Z., Hatipoglu O.F., Ogawa H., Obika M., Ohtsuki T., Inagaki J., Kusachi S., Ninomiya Y.
Organizer
第10回がんとハイポキシア研究会
Place of Presentation
横浜(横浜市開港記念館)
Year and Date
20121206-07
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