The role of netrin, axon guidance factor in melanoma progression focusing the relationship between tumor and blood vessel

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24076
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Kyushu Dental College
• Principal Investigator: Hiromi Honda 九州歯科大学, 歯学部, 助教 (10840085)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: Netrin-1 / Netrin-4 / メラノーマ

Outline of Final Research Achievements

Netrins were originally founded as axon guidance factors in nerve tissue. Recently netrins are known to be expressed by many kinds of cells and have multifunction in physiological and pathological conditions. In this study we examined the relationship between melanoma and Netrin-1 and Netrin-4. Database analysis revealed that the melanoma patients with high expression levels of netrin-1 or netrin 4 tend to have a low survival rate. Treatment of netrin-1 and netrin-4 increased the number of B16 cells. The treatment of murine netrin-1 and netrin-4 also increased the expression levels of cell cycle related genes such as cyclinA2 and cyclinD2. Furthermore, both netrin-1 and netrin-4 promote the migration of B16 cells assessed by wound healing assay.

Free Research Field

口腔保健学

Academic Significance and Societal Importance of the Research Achievements

Netrinがメラノーマの悪性化因子であることを示せれば液性因子であるNetrinに対する中和抗体は有力な治療の候補となり得る．実際，Netrin-1に対する抗体は進行性固形がんに対しての第I相試験が終了している．さらにNetrin-1の発現量と悪性黒色腫の悪性度や予後との相関が明らかになれば，血液中を循環するNetrin-1量をELISA等で定量することで，再発や転移のリスクを反映する有用なバイオマーカーとなる可能性がある．