Aim: 

Human CC chemokine Macrophage Inflammatory Protein-3a (MIP-3a) directs inflammatory cell migration through its binding to the transmembrane receptor CCR6. MIP-3a has recently been shown to promote cell migration by up-regulation of matrix metalloproteinases (MMPs). Aim of this study was to analyze the role of the MIP-3a epithelial normal breast cells in primary culture.

Methods: 

Expression of CCR6 and MIP-3a was analyzed by RT-PCR. Signaling was investigated by Western blotting, proliferation by MTT assays and chemotactic cell migration by wounding assays.

Results: 

Epithelial normal breast cells in primary culture expressed MIP-3a and its CCR6 receptor. MIP-3a activated ERK-1/2 and signi?cantly (P < 0.05) increased cell proliferation. PD98059 inhibited both MIP-3a-mediated ERK-1/2 phosphorylation and cell proliferation, suggesting MEK-1 as upstream signal transducer of ERK-1/2. MIP-3a signi?cantly (P < 0.001) increased cell migration and stimulated the production of both MMP-2 and -9. In addition, we demonstrated that MMPs inhibition signi?cantly (P < 0.05) decreased cell migration stimulated by MIP-3a.

Conclusion: 

These data indicated that MIP-3a, through the CCR6 receptor mediated signals, increased normal breast cells migration and proliferation and suggested that MIP-3a might have an important role in breast homeostasis and in?ammation by mediating chemotaxis. It is suggested that the expression of MIP-3a in normal breast cells could facilitate the migration and invasion of cancer cells into the normal breast epithelium.