Furthermore, “brain-derived soluble factors” upregulate CCR4 expression in melanoma cells and enhance the migration of brain-metastasizing melanoma cells specifically; however, whether these soluble factors are the brain-expressed CCR4 ligands, CCL17 or CCL22, and whether this signaling axis promotes melanoma brain metastasis remains to be determined [23]. This evidence concerns the gene CCR4 and melanoma.