Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 144, Issue 12, Pages 3138-3145Publisher
WILEY
DOI: 10.1002/ijc.31945
Keywords
decoy biologics; A9; metastasis
Categories
Funding
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED) [JP17cm0106216]
- Fujii Memorial Medical Science Foundation
- Kobayashi Foundation for Cancer Research
- Princess Takamatsu Cancer Research Fund
- Takeda Science Foundation
- JSPS KAKENHI [17H03577]
- Grants-in-Aid for Scientific Research [17H03577] Funding Source: KAKEN
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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, NPTN beta, 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.
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