The major causes of cancer deaths are probably due to metastasis to distant organs, and thus effective therapies for metastatic cancer are desired. It is considered that the formation of a premetastatic niche similar to tumor microenvironment promotes metastasis. S100A8, one of endogenous ligands for Toll-like receptor 4 (TLR4), induces the recruitment of bone marrow-derived suppressor cells to the surrounding of tumor and distant organs, which promote metastasis. In addition, the overexpression of TLR4 has been reported in various cancer cells, and the suppression of S100A8 function is expected to inhibit cancer progression and metastasis. We have identified peptides and low-molecular-weight compounds that competitively inhibit the binding of S100A8 to TLR4, and found multivalent S100A8 inhibitory peptides suppress the tumor growth in tumor-bearing mice.
