CXCR4, CCR7 and CCR10
chemokine receptors are known to be involved in
melanoma metastasis. Our goal was to compare the relative intratumoral
mRNA expression of these receptors with that of their corresponding
chemokine ligands, CXCL12, CCL19, CCL21, and CCL27 across the full spectrum of human
melanoma progression: thin and thick primary
melanomas, as well as "in transit", lymph node, and distant
metastases. Expression was quantified by real-time RT-PCR in 103
melanoma samples: 51 primary
tumors and 52
metastases. Particular emphasis was focused on
chemokine ligand-receptor expression ratios. Immunohistochemistry was performed to identify the cell types expressing these molecules. CXCL12-CXCR4 and CCL27-CCR10 ratios were higher in thin than in thick primary
melanomas, and all four
chemokine-receptor ratios were higher in primary
tumors than in
melanoma metastases. CCL27-CCR10 and CXCL12-CXCR4 expression ratios in primary
tumors were inversely associated with the development of distant
metastases, and improved the predictive value of
tumor thickness for distant
metastasis, which is important since
chemokine ligand-receptor ratios are not affected by the endogenous gene employed for normalizing
mRNA expression. Both receptor and
ligand immunolabeling were detected in neoplastic cells suggesting autocrine mechanisms. Our results support the concept that low CCL27/CCR10 and CXCL12/CXCR4 intratumoral
mRNA ratios are associated with
melanoma progression, and in combination with Breslow thickness, are the best predictive factors for the development of distant
metastases in primary cutaneous
melanoma.