Anti-tumor effect of class-3 semaphorins in neuroblastoma

• Project/Area Number: 17K17006
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Nihon University
• Principal Investigator: HOSHI Reina 日本大学, 医学部, 専修医 (20793772)
• Research Collaborator: NAGASAKI Eri
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小児腫瘍学 / 神経芽腫 / Semaphorin / Neuropilin / 細胞浸潤能 / 細胞遊走能 / Integrinβ1 / 医学 / 外科 / 臨床医学

Outline of Final Research Achievements

The class 3 semaphorins (SEMA3s) have been shown to be tumor suppressors in various cancer. Although it has been reported that Neuropilins (NRPs) are expressed at higher levels in neuroblastoma (NB) tissue compared to normal adrenal tissues, the role of their ligand SEMA3s in NB have not yet been elucidated. In the present study, we investigated the role of SEMA3s in NB.
We examined the effects of human recombinant SEMA3A, SEMA3B, SEMA3F on proliferation, migration, and invasion of NB-derived cells. NB-derived SK-N-AS cells exhibited reduced migration when treated with recombinant SEMA3A. The silencing of SEMA3A results in the promotion of the migratory and invasive abilities of SK-N-AS cells, along with the upregulated expression of β1 integrin. The results presented herein indicated that SEMA3A exerts tumor suppressive effects by regulating the expression of β1 integrin in NB.

Academic Significance and Societal Importance of the Research Achievements

神経芽腫は小児の悪性固形腫瘍では脳腫瘍に次いで頻度が高い疾患である。高リスク群の神経芽腫では集学的治療を行っているものの、未だ予後不良であり、新規治療法の開発が喫緊の課題である。本研究結果から、SEMA3Aは神経芽腫においてIntegrinβ1を抑制することで抗腫瘍効果を発揮することが示唆された。このことから、神経芽腫においてSEMA3Aを標的とした新規治療法の可能性が考えられた。

Research Products

• [Journal Article] NRP1 knockdown promotes the migration and invasion of human neuroblastoma-derived SK-N-AS cells via the activation of β1 integrin expression (2018)
  • Author(s): Ishizuka Yoshiaki, Koshinaga Tsugumichi, Hirano Takayuki, Nagasaki-Maeoka Eri, Watanabe Yosuke, Hoshi Reina, Yoshizawa Shinsuke, Sugito Kiminobu, Kawashima Hiroyuki, Uekusa Shota, Fukuda Noboru, Soma Masayoshi, Fujiwara Kyoko
  • Journal Title: International Journal of Oncology Volume: 53 Pages: 159-166
  • DOI: 10.3892/ijo.2018.4397
  • Peer Reviewed