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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: glioblastoma / Wnt-5a / MMP-2 / Fzd2 / Fzd6 / Ryk / Ror2 / invasion / Wnt5a / Frizzled2 / Frizzled6 / Glioblastoma / Survival time / Wnt / Frizzled / 悪性グリオーマ / 膠芽腫 / 増殖 / 浸潤 / 生命予後

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 Volume: 156 Issue: 1 Pages: 29-38
  • DOI: 10.1093/jb/mvu015
  • Peer Reviewed
• [Journal Article] Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older. (2014)
  • Author(s): Yunoue S, Tokimura H, Tominaga A, Fujio S, Karki P, Usui S, Kinoshita Y,Habu M, FM Moinuddin, HiranoH, Arita K
  • Journal Title: Neurosurgical Review Volume: 37 Issue: 2 Pages: 269-277
  • DOI: 10.1007/s10143-013-0509-3
  • Peer Reviewed
• [Journal Article] Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma: evaluative methodology for DAB chromogenic immunostaining. (2013)
  • Author(s): Hirano H, Yonezawa H, Yunoue S, Habu M, Uchida H, Yoshioka T, Kishida S, Kishida M, Oyoshi T, Fujio S, Sugata S, Yamahata H, Hanaya R, Arita K.
  • Journal Title: Brain Tumor Pathology Volume: 31 Issue: 2 Pages: 85-93
  • DOI: 10.1007/s10014-013-0153-1
  • Peer Reviewed
• [Journal Article] Wnt-5a signaling is correlated with infiltrative activity in human glioma by inducing cellular migration and MMP-2 (2011)
  • Author(s): Masayuki Kamino, Michiko Kishida, Toshiro Kibe, Kyoko Ikoma, Mikio Iijima, Hirofumi Hirano, Mai Tokudome, Lin Chen, Chihaya Koriyama, Katsushi Yamada, Kazunori Arita and Shosei Kishida
  • Journal Title: cancer science Volume: 10（3） Pages: 540-548
  • NAID: 10029290969
• [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.)
• [Presentation] Wnt5a, Fzd2, Fzd6, and Ryk expression in glioblastoma (2014)
  • Author(s): Hirofumi H, Hajime Y, Mika H, Shosei K, Shingo F, Kazunori A.
  • Organizer: 82nd AANS Annual Scientific Meeting
  • Place of Presentation: San Francisco, America
• [Presentation] Collagen deposition makes MRI T2 hypointensity of metastatic brain tumors from gastric and colonic cancers (2014)
  • Author(s): Hirofumi H, Shunichi Y, Shunji Y, Hajime Y, Kazutaka Y, Ryosuke H, Hiroshi T, Kazunori A.
  • Organizer: 82nd AANS Annual Scientific Meeting
  • Place of Presentation: San Francisco, America
• [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
• [Presentation] Glioma浸潤活性におけるWnｔシグナルの作用機与 (2011)
  • Author(s): 羽生未佳、神野真幸、岸田想子、岐部俊朗、湯之上俊二、飯島幹雄、平野宏文、岸田昭世、時村洋、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
• [Presentation] GliomaにおけるWnｔシグナル分子の作用機与 (2011)
  • Author(s): 羽生未佳、神野真幸、岸田想子、岐部俊朗、湯之上俊二、飯島幹雄、平野宏文、岸田昭世、時村洋、有田和徳
  • Organizer: 第29回日本脳腫瘍学会学術総会
  • Place of Presentation: 岐阜県下呂温泉 水明館
• [Presentation] RGB3原色分析を用いたDAB発色免疫染色評価
  • Author(s): 平野宏文，米澤 大，湯之上俊二，内田裕之，羽生未佳，義岡孝子，花谷亮典，時村洋，有田和徳
  • Organizer: 第30回日本脳腫瘍病理学会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 膠芽腫におけるWnt5a, Fzd2, Fzd6, Ryk の発現と生存期間への影
  • 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回日本脳腫瘍学会学術集会
  • Place of Presentation: グランドプリンスホテル広島