Netrin-1 as a novel therapeutic target of medulloblastoma

• Project/Area Number: 16K20013
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Hiroshima International University (2017); Ehime University (2016)
• Principal Investigator: Nakayama Hironao 広島国際大学, 保健医療学部, 講師 (40512132)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 軸索誘導因子 / netrin / 髄芽腫 / 転移 / 血管新生 / 癌幹細胞 / Shh

Outline of Final Research Achievements

Netrin-1, a chemoattractant factor in the neuronal system, promotes tumor progression by enhancing angiogenesis and metastasis. Our recent studies demonstrate that netrin-1 promotes medulloblastoma (MB) cell invasiveness and angiogenesis, therefore, we aim to target netrin-1 signaling for MB therapy.
Netrin-1 acts via several receptors, including UNC5A-D, DCC, DSCAM and neogenin. To identify the key netrin receptor in MB, we purified MB cancer stem like cells and carried out microarray. As a result, one of the netrin receptor was elevated in MB cancer stem cells. We will investigate the function of this receptor in MB and expect this receptor as a novel marker of MB stem cell. We will also screen the inhibitor of this receptor and test with MB model mice.

Research Products

• [Journal Article] Cullin 3 regulates ADAMs-mediated ectodomain shedding of amphiregulin (2018)
  • Author(s): Nakayama Hironao、Sakaue Tomohisa、Maekawa Masashi、Fujisaki Ayako、Higashiyama Shigeki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 499 Issue: 1 Pages: 17-23
  • DOI: 10.1016/j.bbrc.2018.03.097
  • Peer Reviewed / Open Access
• [Journal Article] Novel function of axon guidance molecule as a regulator of tumor microenvironment (2017)
  • Author(s): Nakayama H, Higashiyama S.
  • Journal Title: Folia Pharmacologica Japonica Volume: 150 Issue: 6 Pages: 286-292
  • DOI: 10.1254/fpj.150.286
  • NAID: 130006247551
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular NeovascularizationHighlights (2017)
  • Author(s): Inoue Yuki、Shimazawa Masamitsu、Nakamura Shinsuke、Takata Shinsuke、Hashimoto Yuhei、Izawa Hiroshi、Masuda Tomomi、Tsuruma Kazuhiro、Sakaue Tomohisa、Nakayama Hironao、Higashiyama Shigeki、Hara Hideaki
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 38 Issue: 1 Pages: 174-185
  • DOI: 10.1161/atvbaha.117.310337
  • Peer Reviewed
• [Journal Article] Prospect of divergent roles for the CUL3 system in vascular endothelial cell function and angiogenesis (2017)
  • Author(s): Sakaue Tomohisa、Maekawa Masashi、Nakayama Hironao、Higashiyama Shigeki
  • Journal Title: The Journal of Biochemistry Volume: 162 Pages: 237-245
  • DOI: 10.1093/jb/mvx051
  • NAID: 40021380486
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of ANP32B exerts anti-apoptotic effects in hepatocellular carcinoma. (2017)
  • Author(s): Ohno Y, Koizumi M, Nakayama H, Watanabe T, Hirooka M, Tokumoto Y, Kuroda T, Abe M, Fukuda S, Higashiyama S, Kumagi T, Hiasa Y.
  • Journal Title: PLoS One. Volume: 12 Issue: 5 Pages: 0177343-0177343
  • DOI: 10.1371/journal.pone.0177343
  • Peer Reviewed / Open Access
• [Presentation] セマフォリン3Fは乳癌の血管新生と転移を抑制する. (2017)
  • Author(s): 中山寛尚, 村上朱里, 福田尚代, 亀井義明, 高田泰次, 東山繁樹.
  • Organizer: 生命科学系学会合同年次大会 第90回日本生化学会
• [Presentation] Semaphorin 3F inhibits breast tumor angiogenesis and metastasis via Akt-mTOR pathway. (2017)
  • Author(s): Hironao Nakayama, Akari Murakami, Hisayo Nishida-Fukuda, Yoshiaki Kamei, Yasutsugu Takada and Shigeki Higashiyama.
  • Organizer: 第76回日本癌学会学術総会