細胞外マトリックスによるがん血管新生、リンパ管新生制御のメカノバイオロジー

2013 Fiscal Year Annual Research Report

• Project/Area Number: 23612004
• Research Institution: Okayama University
• Principal Investigator: 稲垣 純子 岡山大学, 医歯(薬)学総合研究科, 助教 (90271056)
• Co-Investigator(Kenkyū-buntansha): 廣畑 聡 岡山大学, 国際センター, 准教授 (90332791) ; 二宮 善文 岡山大学, 医歯(薬)学総合研究科, 教授 (70126241)
• Keywords: ADAMTS1 / 細胞外マトリックス / がん内圧 / 血管新生 / リンパ管新生

Research Abstract

ADAMTS1 がヒト臍帯静脈内皮細胞（HUVEC）のみならずヒト皮膚微小リンパ管内皮細胞（HMVEC-dLy）においても増殖・管腔形成を阻害することを発見し、その抑制効果はADAMTS1が直接VEGFCと結合することによってもたらされていることを明らかにした（Experimental Cell Research, 2014; 323: 263-75）。これらの結果より、ADAMTS1が、がんの血管新生のみならずリンパ管新生においても重要な役割を担っていることが示された。
さらに、我々はIFPの増大する腫瘍にVEGFCを投与しリンパ管新生を促した結果、腫瘍増大が抑制される結果を得た（Transl Oncol. 2013; 6(4): 398-404）。興味深いことにVEGFA では抗腫瘍効果は認められず、むしろ腫瘍は増大した。つまり、VEGFCにより形成されたリンパ管網がIFPを低下させるドレナージ効果を発揮したと言え、IFPを低下させるドレナージ療法は、がんの新たな治療法となり得る可能性を示している。

Research Products

• [Journal Article] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor. (2014)
  • Author(s): Inagaki J, Takahashi K, Ogawa H, Asano K, Faruk Hatipoglu O, Cilek MZ, Obika M, Ohtsuki T, Hofmann M, Kusachi S, Ninomiya Y, Hirohata S.
  • Journal Title: Exp Cell Res. Volume: 323 Pages: 263-275
  • DOI: 10.1016/j.yexcr.2014.03.002
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor C-induced lymphangiogenesis decreases tumor interstitial fluid pressure and tumor. (2013)
  • Author(s): Hofmann M, Pflanzer R, Zoller NN, Bernd A, Kaufmann R, Thaci D, Bereiter-Hahn J, Hirohata S, Kippenberger S.
  • Journal Title: Transl Oncol. Volume: 6(4) Pages: 398-404
  • DOI: 10.1593/tlo.13274
  • Peer Reviewed
• [Presentation] Short period Hyaluronan treatment reduced cartilage degradation in rat osteoarthritis model (2014)
  • Author(s): Takashi Ohtsuki, Satoshi Hirohata, Yuri Shoji, Keiichi Asano, Aya Hirata, Teruyuki Kawadi, Junko Ingaki, Kanae Kumagishi, Keiichiro Nishida, Yoshifumi Ninomiya
  • Organizer: Joint Conference of 46th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR), and 61th Annual Meeting of the Japan Matrix Club (JMC)
  • Place of Presentation: WINK AICHI
  • Year and Date: 20140605-20140607
• [Presentation] ADAMTS1 binds to VEGFC and inhibits lymphangiogenesis (2014)
  • Author(s): Junko Inagaki, Katsuyuki Takahashi, Hiroko Ogawa, Keiichi Asano, Omer F. Hatipoglu, Mehmet Zeynel Cilek, Masanari Obika, Takashi Ohtsuki, Matthias Hofmann, Shozo Kusachi, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: Joint Conference of 46th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR), and 61th Annual Meeting of the Japan Matrix Club (JMC)
  • Place of Presentation: WINK AICHI
  • Year and Date: 20140605-20140607
• [Presentation] Versicanolysis in Breast cancer in tumor-baring mice model (2014)
  • Author(s): Keiichi Asano, Junko Inagaki, Matthias Hofmann, Teruyuki Kawadi, Aya Hirata, Takashi Ohtsuki, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: Joint Conference of 46th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR), and 61th Annual Meeting of the Japan Matrix Club (JMC)
  • Place of Presentation: WINK AICHI
  • Year and Date: 20140605-20140607
• [Presentation] Cyclic tensile strain (CTS) down-regulates interleukin(IL)-1β and Tumor necrosis factor(TNF)-α induced matrix degrading enzymes mRNA expression in human chondrosarcoma cell line OUMS-27 by mechano sensor (2014)
  • Author(s): Takashi Ohtsuki, Teruyuki Kawadi, Aya Hirata, Keiichi Asano, Eriko Kusunoki, Junko Inagaki, Kanae Kumagishi, Keiichiro Nishida, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 2nd International Symposium on Mechanobiology
  • Place of Presentation: Okayama university Junko Fukutake Hall
  • Year and Date: 20140520-20140523
• [Presentation] ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor (2014)
  • Author(s): Junko Inagaki, Katsuyuki Takahashi, Hiroko Ogawa, Omer Hatipoglu, Mehmet Cilek, Masanari Obika, Takashi Ohtsuki, Shozo Kusachi, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: Kyoto Miyakomesse
  • Year and Date: 20140414-20140417
• [Presentation] Inflammatory cytokine induced Hyaluronan synthases under hyaluronan treatment in human chondrosarcoma cell line OUMS-27 cells (2014)
  • Author(s): Takashi Ohtsuki, Teruyuki Kawadi, Aya Hirata, Keiichi Asano, Eriko Kusunoki, Junko Inagaki, Kanae Kumagishi, Keiichiro Nishida, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 27th Annual meeting of the Japanese Society of Cartilage metabolism
  • Place of Presentation: Kyoto Medical Association Center
  • Year and Date: 20140228-20140302
• [Presentation] Cyclic tensile strain (CTS) inhibits Interleukin-1β and Tumor Necrosis Factor-α induced catalytic reactions in human chondrosarcoma cell line OUMS-27-microRNA array analysis- (2013)
  • Author(s): Takashi Ohtsuki, Teruyuki Kawadi, Aya Hirata, Keiichi Asano, Eriko Kusunoki, Junko Inagaki, Kanae Kumagishi, Keiichiro Nishida, Yoshifumi Ninomiya, Satoshi Hirohata
  • Organizer: The 36th Annual meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe convention center
  • Year and Date: 20131203-20131206