Amersi FF et al. (2008) Activation of CCR9/CCL25 in cutaneous melanoma mediates preferential metastasis to the small intestine. Clin Cancer Res 14: 638–645

Evidence is accumulating to indicate that chemokines might have a role in tumor-cell trafficking. Recent studies have shown that CCL25—which mediates the chemotaxis of CCR9+ cells—is an important chemokine involved in cellular homing to the small intestine. On the basis of these data, Amersi et al. hypothesized that chemokine-mediated homing via the CCR9–CCL25 axis might be the primary mechanism by which cutaneous melanomas preferentially metastasize to the small intestine.

The quantification of CCR9 mRNA levels in 23 metastatic melanoma lines reinforced the evidence for a specific role of the CCR9–CCL25 axis in tumor-cell migration to the small intestine: of the 23 metastatic lines tested, only the 8 lines derived from small intestinal metastases expressed CCR9. The expression of CCR9 was then examined in specimens from 198 patients who had undergone resection of metastatic melanoma. Among the 102 specimens from small intestinal metastases, 86% expressed CCR9. None of the specimens from patients who had undergone resection for cutaneous melanoma metastasis to organs other than the small intestine expressed CCR9. Furthermore, no notable immunohistochemical staining for CCR9 was seen in melanoma metastases to organs other than the small intestine. Cell-migration and cell-invasion assays revealed that CCL25 could induce the migration of four CCR9+ melanoma cell lines; CCR9− cells did not respond to CCL25, and pretreatment of CCR9+ lines with an anti-CCR9 antibody prevented migration.

The authors conclude that tumor-cell migration along the CCR9–CCL25 axis might explain the distinct pattern of metastasis to the small intestine observed with cutaneous melanoma.