The role of netrin, axon guidance factor in melanoma progression focusing the relationship between tumor and blood vessel
| Project/Area Number |
19K24076
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0907:Oral science and related fields
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
Hiromi Honda 九州歯科大学, 歯学部, 助教 (10840085)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Netrin-1 / Netrin-4 / メラノーマ / Netrin1 / Netrin4 / 悪性黒色腫 / 細胞増殖 / 細胞移動 / 転移 / Netrin / 血管内皮細胞 |
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| Outline of Research at the Start |
悪性腫瘍では腫瘍の成長に伴い、腫瘍細胞、血管内皮細胞、さらにこれらの細胞を支持する間質細胞から構成される腫瘍(がん)微小環境が構築される。この腫瘍微小環境内では細胞間同士がコミュニケーションをとり、腫瘍の増殖・浸潤・転移を制御する。Netrin-1, 4は多くの悪性腫瘍細胞の移動・浸潤に関わるが、悪性黒色腫におけるNetrin-1, 4の役割には不明な点が多い。われわれ研究チームはこれまでに血管内皮細胞からNterin-1, 4が分泌されることを見出している。そこで本研究では、悪性黒色腫の腫瘍微小環境における血管内皮細胞から分泌されるNetrin-1, 4の役割を明らかにする。
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| 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.
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| 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．
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Transducin-like enhancer of split 3 regulates proliferation of melanoma cells via histone deacetylase activity2019
Author(s)
Ogawa M, Yaginuma T, Nakatomi C, Nakajima T, Tada-Shigeyama Y, Addison WN, Urata M, Matsubara T, Watanabe K, Matsuo K, Sato T, Honda H, Hikiji H, Watanabe S, Kokabu S
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Journal Title
Oncotarget
Volume: 10
Pages: 404-414
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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