ExSSSRs (extracellular S100 soil sensor receptors)‐Fc fusion proteins work as prominent decoys to S100A8/A9‐induced lung tropic cancer metastasis. Issue 12 (4th December 2018) - Kinoshita, Rie
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". Abstract : What's new? The heterodimer complex S100A8/A9 is a suspected mediator of organ tropic metastasis, whereby tumor cells, or "seeds, " spread to preferred organ, or "soil, " sites as cancer progresses. Here, the S100 soil sensor receptors (SSSRs) EMMPRIN, NPTNβ, MCAM, and ALCAM, which display different expression patterns depending on cancer type, were investigated for their ability to serve as decoys to prevent S100A8/A9 binding to endogenous SSSRs. In experiments in cancer cells and in a lung metastasis model in vivo, purified chimera decoy SSSR proteins successfully suppressed S100A8/A9‐mediated metastasis. The findings warrant further investigation of SSSR biologics for the prevention of cancer metastasis.