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 Ruma; Hiromasa Yamamoto; Junichi Soh; Toshihiko Hibino; Masahiro Nishibori; Eisaku Kondo; Shinichi Toyooka; Masakiyo Sakaguchi

doi:10.1002/ijc.31945

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

Int J Cancer. 2019 Jun 15;144(12):3138-3145. doi: 10.1002/ijc.31945. Epub 2018 Dec 4.

Authors

Rie Kinoshita¹, Hiroki Sato², Akira Yamauchi³, Yuta Takahashi², Yusuke Inoue⁴, I Wayan Sumardika^{1

5}, Youyi Chen¹, Nahoko Tomonobu¹, Kota Araki², Kazuhiko Shien², Shuta Tomida⁶, Hidejiro Torigoe², Kei Namba², Eisuke Kurihara², Yusuke Ogoshi², Hitoshi Murata¹, Ken-Ichi Yamamoto¹, Junichiro Futami⁷, Endy Widya Putranto⁸, I Made Winarsa Ruma^{1

5}, Hiromasa Yamamoto², Junichi Soh², Toshihiko Hibino⁹, Masahiro Nishibori¹⁰, Eisaku Kondo¹¹, Shinichi Toyooka², Masakiyo Sakaguchi¹

Affiliations

¹ Departments of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
² Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
³ Department of Biochemistry, Kawasaki Medical School, Okayama, Japan.
⁴ Faculty of Science and Technology, Division of Molecular Science, Gunma University, Gunma, Japan.
⁵ Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.
⁶ Departments of Bioinformatics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁷ Departments of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan.
⁸ Department of Child Health, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.
⁹ Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
¹⁰ Departments of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹¹ Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and dental Sciences, Niigata, Japan.

PMID: 30365872
DOI: 10.1002/ijc.31945

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".

Keywords: S100A8/A9; decoy biologics; metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basigin / chemistry
Basigin / pharmacology
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Calgranulin A / metabolism*
Calgranulin B / metabolism*
Cell Adhesion Molecules / chemistry
Cell Adhesion Molecules / pharmacology
Humans
Immunoglobulin Fc Fragments / chemistry
Immunoglobulin Fc Fragments / pharmacology
Immunoglobulin G / immunology
Lung Neoplasms / drug therapy
Lung Neoplasms / metabolism
Lung Neoplasms / secondary
Melanoma, Experimental / metabolism
Melanoma, Experimental / pathology
Melanoma, Experimental / prevention & control*
Melanoma, Experimental / secondary*
Mice
Mice, Inbred BALB C
Mice, Nude
Protein Domains
Receptor for Advanced Glycation End Products / chemistry
Recombinant Fusion Proteins / isolation & purification
Recombinant Fusion Proteins / metabolism
Recombinant Fusion Proteins / pharmacology*

Substances

Calgranulin A
Calgranulin B
Cell Adhesion Molecules
Immunoglobulin Fc Fragments
Immunoglobulin G
Receptor for Advanced Glycation End Products
Recombinant Fusion Proteins
Basigin