The role of the G-protein coupled receptor C-C chemokine receptor 7 in T lymphocyte migration and breast cancer metastasis

C-C Chemokine Receptor 7 (CCR7) promotes migration of T lymphocytes into and throughout lymph nodes via ligands CCL21 and CCL19. The mechanisms by which CCR7 directs T lymphocyte trafficking are unknown. Using migration and western assays we identified that migration to CCL21 required activation of G&agr;i, phosphorylation of ERK2 and PLCgamma1. We found by RT-PCR that CCL19 treatment increased S1P1 receptor mRNA and activated ERK5, which was required for lymph node exit. CCR7 is also expressed in metastatic breast cancer, yet it remains unclear if CCR7 mediates metastasis to lymph nodes. We developed a mouse model and found that CCR7 promoted lymph node metastasis and concomitantly reduced metastasis to lungs. This work has defined additional and novel molecular mechanisms required for CCR7 mediated migration in T lymphocytes. Further, we have learned that CCR7 promotes breast cancer metastasis to lymph nodes in vivo while reducing metastasis to other organs.