Abstract 1390: Endothelin-1/ETBR axis promote COX-2 production and migration in human chondrosarcoma cells through MAPK and AP-1 pathways

Abstract

Abstract Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Endothelin-1 (ET-1) the most potent vasoconstrictor, plays a crucial role in migration and metastasis of human cancer cells. Cyclooxygenase (COX)-2 has been implicated in tumor metastasis. However, the effects of ET-1 in migration and COX-2 expression in chondrosarcoma cells are largely unknown. The aim of this study was to investigate whether ET-1 is associated with the motility of human chondrosarcoma cell. We found that treatment of human chondrosarcoma cells (JJ012 cells) with ET-1 increased migration and expression of COX-2. Activations of MAPK (p38, JNK and ERK) and activator protein-1 (AP-1) pathways after ET-1 treatment were demonstrated, and ET-1-induced expression of COX-2 and migration activity was inhibited by the specific inhibitor and mutant of Endothelin B receptor (ETBR), MAPK and AP-1 cascades. Moreover, ET-1 increased the binding of c-Jun to the AP-1 element on the COX-2 promoter. ETBR and MAPK inhibitor reduced ET-1 mediated binding activity and AP-1 luciferase activity. Taken together, our results indicated that ET-1 enhances the migration of chondrosarcoma cells by increasing COX-2 expression through the ETBR axis, MAPK and AP-1 signal transduction pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1390. doi:10.1158/1538-7445.AM2011-1390