The Endothelin Axis Stimulates the Expression of Pro-Inflammatory Cytokines and Pro-Migratory Molecules in Breast Cancer

We investigated the effects of the endothelin-1 (ET-1) receptor dual antagonist (Bosentan (R)) on the inflammatory cytokines and the chemoattractant molecules associated with breast cancer growth and the development of tumor infiltration in bone explants. Immunocompetent mice implanted with the murine mammary carcinoma 4T1 cells in a skin-fold chamber and treated with Bosentan (R) had reduced tumor growth (p < .05). ET-1 promoted the secretion of the anti-inflammatory soluble tumor necrosis factor (TNF) receptor and IL12 p40 in vitro. The Bosentan (R) treatment in vivo was associated with a local increase of the anti-inflammatory IL-1 alpha cytokine concentration and decrease of the pro-inflammatory TNF-alpha and IL-17 cytokine concentrations (p < .05).