Chemokine–chemokine receptor axes in melanoma brain metastasis

Emerging findings into molecular mechanism of brain metastasis

“…Izraely discovered that brain‐metastasizing melanoma cells expressed really higher level of C‐C motif chemokine receptor 4 (CCR4). Moreover, “brain‐derived soluble factors” could upregulate CCR4 expression in melanoma cells and facilitate the migration of brain‐metastasizing melanoma cells specifically 92. Recently, a crucial relationship between several altered C‐C motif receptor 4 (CCR4) ligands, including C‐C motif ligand 4/17/22 (CCL4/17/22) and poor clinical outcomes have been observed.…”

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“…Other genes such as ITGA4, CLDN1, CYR61, CDH1, and IL6R are aberrantly down-regulated in brain metastases [8,9]. Our functional studies indicated that claudin-1 (CLDN1) is a MBM suppressor [10] and recently that CCR4 is a MBM promoter [11].…”

“…CLDN1 expression was analyzed by monoclonal anti-human CLDN1 Ab (1μg/sample, R&D Systems), using flow cytometry as described previously [9]. Fluorescein isothiocyanate (FITC)-conjugated goat antirat IgG (1:50, Jackson ImmunoResearch Laboratories) was used as secondary Ab.…”

PAX3 and FOXD3 Promote CXCR4 Expression in Melanoma

“…Recently, expression of CXCR7 was found through candidate gene RT-PCR and RNAseq analysis in human melanoma cell lines (52,53), as well as medaka aquarium fish melanomas (54) and normal melanocytes (55). Furthermore, CXCR7 is necessary for melanocyte and medaka melanoma SDF1-dependent migration (54,55).…”

“…Furthermore, there is some suggestion of cross-talk between receptors in other cell types, and CXCR7 may be affected by changes in CXCR4 levels. Only limited studies now exist that examine CXCR7 in melanoma (52,54) and this receptor may complicate clinical approaches to CXCR4-specific therapeutic targeting.…”