exSSSRs (extracellular S100 soil sensor receptors)-Fc fusion proteins work as prominent decoys to S100A8/A9-induced lung tropic cancer metastasis

Rie Kinoshita, Hiroki Sato, Akira Yamauchi, Yuta Takahashi, Yusuke Inoue, I. Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Kota Araki, Kazuhiko Shien, Shuta Tomida, Hidejiro Torigoe, Kei Namba, Eisuke Kurihara, Yusuke Ogoshi, Hitoshi Murata, Ken-ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I. Made Winarsa RumaHiromasa Yamamoto, Junichi Sou, Toshihiko Hibino, Masahiro Nishibori, Eisaku Kondo, Shinichi Toyooka, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Within the “seed and soil” theory of organ tropic cancer metastasis is a growing compilation of evidence that S100A8/A9 functions as a soil signal that attracts cancer cells to certain organs, which prove beneficial to their growth. S100A8/A9-sensing receptors including Toll-like receptor 4 (TLR4), advanced glycation end products (RAGE), and also important receptors we recently succeeded in identifying (EMMPRIN, NPTNβ, MCAM, and ALCAM) have the potential to become promising therapeutic targets. In our study, we prepared extracellular regions of these novel molecules and fused them to human IgG2-Fc to extend half-life expectancy, and we evaluated the anti-metastatic effects of the purified decoy proteins on metastatic cancer cells. The purified proteins markedly suppressed S100A8/A9-mediated lung tropic cancer metastasis. We hence expect that our novel biologics may become a prominent medicine to prevent cancer metastasis in clinical settings through cutting the linkage between “seed and soil”.

Original languageEnglish
Pages (from-to)3138-3145
Number of pages8
JournalInternational Journal of Cancer
Volume144
Issue number12
DOIs
Publication statusPublished - Jun 15 2019

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Keywords

  • decoy biologics
  • metastasis
  • S100A8/A9

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kinoshita, R., Sato, H., Yamauchi, A., Takahashi, Y., Inoue, Y., Sumardika, I. W., Chen, Y., Tomonobu, N., Araki, K., Shien, K., Tomida, S., Torigoe, H., Namba, K., Kurihara, E., Ogoshi, Y., Murata, H., Yamamoto, K., Futami, J., Putranto, E. W., ... Sakaguchi, M. (2019). exSSSRs (extracellular S100 soil sensor receptors)-Fc fusion proteins work as prominent decoys to S100A8/A9-induced lung tropic cancer metastasis. International Journal of Cancer, 144(12), 3138-3145. https://doi.org/10.1002/ijc.31945