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The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approaches to regulate metastasis is required to overcome the melanoma disease. An accumulating mass of evidence has indicated a critical role of extracellular S100A8/A9 in melanoma distant metastasis. Lung S100A8/A9 is induced by melanoma cells from distant organs and it attracts these cells to its enriched lung environment since melanoma cells possess several receptors that sense the S100A8/A9 ligand. We hence aimed to develop a neutralizing antibody against S100A8/A9 that would efficiently block melanoma lung metastasis. Our protocol provided us with one prominent antibody, Ab45 that efficiently suppressed not only S100A8/A9‐mediated melanoma mobility but also lung tropic melanoma metastasis in a mouse model. This prompted us to make chimeric Ab45, a chimera antibody consisting of mouse Ab45‐Fab and human IgG2‐Fc. Chimeric Ab45 also showed significant inhibition of the lung metastasis of melanoma. From these results, we have high hopes that the newly produced antibody will become a potential biological tool to block melanoma metastasis in future clinical settings. What's new? A new antibody could help stop lung metastasis of melanoma. The S100A8/A9 heterodimer mediates the establishment of lung metastases, and in this paper, the authors set out to develop a neutralizing antibody against it. The antibody they came up with, Ab45, inhibits melanoma mobility and lung metastasis in a mouse model. They then created a chimera of mouse Ab45‐Fab and human IgG2‐Fc. This chimeric Ab45 also successfully thwarted lung metastases, suggesting the new antibody may find a role in human treatments. [ABSTRACT FROM AUTHOR]

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". 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. [ABSTRACT FROM AUTHOR]