2021 Fiscal Year Final Research Report
Canine melanoma-specific activating signals as anti-cancer therapeutic targets: regulation of ERK5 signaling pathway
| Project/Area Number |
19K06389
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
杉谷 博士 日本大学, 生物資源科学部, 教授 (20050114)
中野 令 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (60755619)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 口腔内悪性黒色腫 / イヌ / インターロイキン1β / COX-2 / MAPキナーゼ / ERK5 / MMP-3 / GLUT |
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| Outline of Final Research Achievements |
The inflammatory micro environment in tumors influences tumor growth and metastasis. We investigated intracellular signaling systems mediated by the inflammatory cytokine interleukin-1β (IL-1β) in canine melanoma cells to elucidate cancer-specific signaling systems and explore new cancer therapy. In the melanoma cells IL-1β provoked expression and release matrix metalloprotease 3 (MMP-3), which stimulated chemotaxis. IL-1β also stimulated cyclo-oxygenase 2 (COX-2) expression and prostaglandin E2 release in the melanoma cells. The MAP kinase ERK5 has been suggested to be involved in the IL-1β-induced COX-2 expression. Further, GLUT1 and GLUT3, glucose transporters, have been suggested to be implicated in cell growth via uptake glucose into the melanoma cells, though IL-1β failed to induce expression of those glucose transporters. Together, such cancer specific intracellular signaling and proteins may be new therapy targets for malignant melanoma in dogs.
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| Free Research Field |
獣医学
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| Academic Significance and Societal Importance of the Research Achievements |
悪性黒色腫（メラノーマ）はイヌの口腔内悪性腫瘍で最も発生頻度が高く，また，致死的な腫瘍疾患である。また，イヌメラノーマは増殖，浸潤，転移が非常に速く，診断時には既存の抗腫瘍治療（外科手術，抗がん剤）が不適応となることが多い。本研究では，イヌメラノーマ細胞において腫瘍悪性化の一要因である炎症下で活性化される転写調節や細胞内シグナル分子を明らかにした。これらのイヌメラノーマでの特異性は，新規治療法の標的となることが考えられることから，本研究成果は獣医療学的に大きな意義を有する。
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