Abstract #1162: Dual endothelin receptor antagonist treatment and inflammation in an immuno-competent model of breast cancer bone metastases

Abstract

We investigated the effects of endothelin-1 antagonists on the inflammation associated with breast cancer growth and the development of bone metastases. Murine mammary carcinoma 4T1 cells were injected in a skin-fold chamber implanted with bone explants on immuno-competent CB6 mice. Mice were treated with or without antagonists of ETRA, ETRB or both ET-1 receptors. The development of bone metastases was assessed by histological studies and the presence of cytokeratin-19 in bone explants. Inflammation was assessed by the presence of CD45+ and CD68+ cells in the tumor and bone. In addition, cytokine concentrations, present in tumor and bone samples, were assessed by ELISA. Results indicate that treatment with the ETBR antagonist was associated with significantly reduced tumor mass and tumor bone metastases. However, the observed inflammation was reduced by both treatment as measured by the number of macrophage / monocytes present (P<0.05). In addition, locally in both tumor and bone, ETRA antagonist treatments led to decreased expression of inflammatory cytokines (p<0.05). Furthermore, the changes in inflammation were correlated with smaller tumors and reduced bone invasion (p<0.05). Our data support the hypothesis that through ET-1 may promote the inflammation associated with the development of breast metastases to bone.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1162.