| Affiliation: | 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. Departments of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan 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. Departments of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;10. Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and dental Sciences, Niigata, Japan |
| 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”. |
