S100A8/A9 proteins mediate these effects by binding to plasma membrane elements, including heparan sulfate proteoglycan (HSPG),169 N-glycans,170 TLR4,171 and RAGE.172,173 In a melanoma lung metastasis model, Hiratsuka et al. clearly demonstrated that lung S100A8/A9, as a strong chemokine, interacts with TLR4 on melanoma to attract distant cancer cells to the lungs.174 Recently, it has also been shown that CD146, on melanoma and breast cancer, can respond to lung S100A8/A9 to induce lung-specific metastasis of melanoma175,176 and breast cancer.177. This evidence concerns the gene TLR4 and cancer.