EDN1 and cancer: In contrast to osteolytic cancers, osteoblastic cancer cells increase OB activity and decrease OCL formation and/or activity.90 Endothelin-1 (ET-1), a 21-amino acid peptide released from endothelial cells under steady-state conditions and hypersecreted by tumor cells, is a known regulator of OB function and a potent contributor to cancer-induced nociception.33,66,99 In cocultures of human osteoblastic prostate cancer cells with bone slices, osteoclastic bone resorption is significantly attenuated, an effect which could be rescued after application of an ET-1 neutralizing antibody.