New anti-glioma treatment strategy by clarification of dominant Wnt/Frizzled message

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Kagoshima University
• Principal Investigator: HIRANO Hirofumi 鹿児島大学, 医学部・歯学部附属病院, 講師 (00264416)
• Co-Investigator(Kenkyū-buntansha): KISHIDA Shosei 鹿児島大学, 医歯学総合研究科, 教授 (50274064) ; ARITA Kazunori 鹿児島大学, 医歯学総合研究科, 教授 (90212646) ; YUNOUE Shunji 鹿児島大学, 医歯学総合研究科, 客員研究員 (20404478)
• Project Period (FY): 2011 – 2013
• Keywords: glioblastoma / Wnt-5a / MMP-2 / Fzd2 / Fzd6 / Ryk / Ror2 / invasion

Research Abstract

Glioblastoma, one of the most malignant brain tumors, invade surrounding brain by expression of MMPs. Wnts, secretory proteins bind to their receptors, Fzd, Ror2, and Ryk. We previously reported that Wnt-5a was highly expressed and it up-regulated MMP-2 in glioblastoma.
In this work, we revealed that tumor cell invasion by MMP-2 was achieved via receptor Ryk, and the degree of histological malignancy correlated with expression of Fzd2 and Ryk (J Biochem 2014, doi: 10.1093/jb/mvu015). In another analysis, we reported that high expression of Fzd2 and Fzd6 was poor prognostic factor in glioblastoma patients (Brain Tumor Pathol 2013, 10.1007/s10014-013-0153-1).

Research Products

• [Journal Article] Ryk is essential for Wnt-5a-dependent invasiveness in human glioma (2014)
  • Author(s): Mika Habu, Hirofumi Koyama, Michiko Kishida, Masayuki Kamino, Mikio Iijima, Takao Fuchigami, Hiroshi Tokimura, Masahiro Ueda, Mai Tokudome, Chihaya Koriyama, Hirofumi Hirano, Kazunori Arita, Shosei Kishida
  • Journal Title: J Biochem
  • DOI: 10.1093/jb/mvu015
  • Peer Reviewed
• [Journal Article] Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma : evaluative methodology for DAB chromogenic immunostaining (2014)
  • Author(s): Hirofumi Hirano, Hajime Yonezawa, Shunji Yunoue, Mika Habu, Hiroyuki Uchida, Takako Yoshioka, Shosei Kishida, Michiko Kishida, Tatsuki Oyoshi, Shingo Fujio, Sei Sugata, Hitoshi Yamahata, Ryousuke Hanaya, Kazunori Arita
  • Journal Title: Brain Tumor Pathol Volume: vol.31(2) Pages: 85-93
  • DOI: 10.1007/s10014-013-0153-1
  • Peer Reviewed
• [Presentation] Wnt5a, Fzd2, Fzd6, and Ryk expression in glioblastoma (2014)
  • Author(s): Hirofumi Hirano, Hajime Yonezawa, Mika Habu, Shosei Kishida, Shingo Fujio, Kazunori Arita
  • Organizer: 82nd AANS Annual Scientific Meeting
  • Place of Presentation: Moscone Center(U.S.A.)
  • Year and Date: 20140405-06
• [Presentation] 膠芽腫におけるWnt5a, Fzd2, Fzd6, Rykの発現と生存期間への影響 (2012)
  • Author(s): 平野宏文,羽生未佳,米澤大,湯之上俊二,内田裕之,岸田昭世,花谷亮典,時村洋,有田和徳
  • Organizer: 第30回日本脳腫瘍学会
  • Place of Presentation: グランドプリンスホテル広島
  • Year and Date: 2012-11-26
• [Presentation] Glioma浸潤活性におけるWntシグナルの作用機序 (2011)
  • Author(s): 羽生未佳,神野真幸,岸田想子,岐部俊郎,平野宏文,岸田昭世,有田和徳
  • Organizer: 第12回日本分子脳神経外科学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-10-15