2019 Fiscal Year Final Research Report

Mechanistic analysis of an unidentified downstream signals of S100A8/A9 receptors that play a crucial role in acquisition of metastatic force and formation of cancer microenvironment.

Research Project

PDF

Project/Area Number	17H03577
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Tumor biology
Research Institution	Okayama University
Principal Investigator	Sakaguchi Masakiyo 岡山大学, 医歯薬学総合研究科, 教授 (70379840)
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)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	炎症 / がん / S100A8/A9 / S100A8/A9受容体 / 転移
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.
Free Research Field	細胞生物学
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。