Background: Liver metastasis is associated with a proinflammatory microenvironment and up-regulation of cell adhesion molecules expressed by endothelial cells. The aim of this study was to characterize the interrelations between breast cancer cell-secreted cytokines, macrophages and E-selectin-mediated cancer cell adhesion and their role in metastasis of breast cancer.
Materials and methods: Three metastatic breast cancer cell lines (1590, KM22, ZE) were studied. Cell culture supernatants were screened for cytokines and the potential for cytokines to increase tumor-necrosis factor-α (TNF-α) production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell adhesion of fluorescence labelled tumor cells was evaluated by measurement of fluorescence intensity with and without E-selectin-blocking strategies (monoclonal antibodies, cimetidine).
Results: Tumor-specific cytokine secretion patterns were revealed. TNF-α secretion from cultured macrophages increased after incubation with tumor supernatants. Tumor cell adhesion was significantly inhibited by cimetidine and monoclonal antibodies against E-selectin (KM22 with cimetidine, p<0.05).
Conclusion: Breast cancer cell-secreted cytokines stimulate macrophages to produce TNF-α, a known up-regulator of E-selectin expression, and therefore cell adherence to endothelium. Inhibition of this mechanism could be an attractive therapeutic option for the prevention of breast cnacer metastasis.