IDENTIFICATION OF ENDOTHELIN-1 IN THE PATHOPHYSIOLOGY OF METASTATIC ADENOCARCINOMA OF THE PROSTATE

Prostate cancer is the second most common cause of death from cancer i n U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly k nown as a potent vasoconstrictor, is a normal ejaculate protein that a lso stimulates osteoblasts. We show here that plasma immunoreactive en dothelin concentrations are significantly elevated in men with metasta tic prostate cancer and that every human prostate cancer cell line tes ted produces endothelin-1 messenger RNA and secretes immunoreactive en dothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, in dicating that ectopic endothelin-1 may be a mediator of the osteoblast ic response of bone to metastatic prostate cancer.