| Project/Area Number |
17H03577
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 健一 岡山大学, 医歯薬学総合研究科, 助教 (00711798)
冨田 秀太 岡山大学, 医歯薬学総合研究科, 准教授 (10372111)
豊岡 伸一 岡山大学, 医歯薬学総合研究科, 教授 (30397880)
木下 理恵 岡山大学, 医歯薬学総合研究科, 助教 (40518297)
村田 等 岡山大学, 医歯薬学総合研究科, 講師 (90579096)
枝園 和彦 岡山大学, 大学病院, 助教 (30708079)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 炎症 / がん / S100A8/A9 / S100A8/A9受容体 / 転移 |
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| Outline of Final Research Achievements |
We found that MCAM among the S100 soil sensor receptors (SSSRs) were highly expressed in melanoma cells and breast cancer cells in a constant manner. On the other hand, NPTNβ was overexpressed in lung cancer cells. Our efforts in studying MCAM- and NPTNβ-downstream signal pathway(s) that should supply metastatic forces to cancer cells upon S100A8/A9 binding gave us the identification of the important signal axis, that is, MCAM-TPL2-ETV4 and RAS/TRAF2-NFIA/NFIB-SPDEF cascades, respectively. When we blockaded these signal pathways, the cancer metastasis was significantly downregulated in melanoma, breast cancer and lung cancer cells in vivo. These results indicate that the identified pathways play a crucial part in cancer metastasis in settings at not only in vitro but also in vivo.
In conclusion, we succeeded to identify MCAM and NPTNβ downstream pathways that have not been understood in detail so far. The identified pathways supply cancer cells a strong metastatic force.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、これまで、S100A8/A9とS100A8/A9新規受容体群との連携をブロックする製剤を開発し、種々がん細胞の浸潤、転移抑制に絶大な効果を示すことを報告してきた。本研究成果（受容体群の転移動力を生み出す信号伝達機序の解明に成功）は、学術上重要な意義を有することはもちろん、先行の開発製剤効能の土台をゆるがない強固なものにすることから医療応用面でも大きな意義を有する。
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