title: A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases.
abstract: Osteoblastic bone metastases are common in prostate and breast cancer patients, but mechanisms by which tumor cells stimulate new bone formation are unclear. We identified three breast cancer cell lines that cause osteoblastic metastases in a mouse model and secrete endothelin-1. Tumor-produced endothelin-1 stimulates new bone formation in vitro and osteoblastic metastases in vivo via the endothelin A receptor. Treatment with an orally active endothelin A receptor antagonist dramatically decreased bone metastases and tumor burden in mice inoculated with ZR-75-1 cells. Tumor-produced endothelin-1 may have a major role in the establishment of osteoblastic bone metastases, and endothelin A receptor blockade represents effective treatment.
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center, Institute for Drug Development, 14960 Omicron Drive, San Antonio, TX 78245, USA.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Yin
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Mohammad
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Käkönen
authors.forename: Stephen
authors.initials: S
authors.lastname: Harris
authors.forename: J Ruth
authors.initials: JR
authors.lastname: Wu-Wong
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Wessale
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Padley
authors.forename: I Ross
authors.initials: IR
authors.lastname: Garrett
authors.forename: John M
authors.initials: JM
authors.lastname: Chirgwin
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Guise
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary*; D016723:Bone Remodeling / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology*; D014407:Tumor Cells, Cultured
chemical_list: D019332:Endothelin-1