Nature Medicine
1, 944 - 949 (1995)
doi:10.1038/nm0995-944
Identification of endothelin−1 in the pathophysiology of metastatic adenocarcinoma of the prostateJoel B. Nelson1, 4, Sean P. Hedican1, Daniel J. George2, A. H. Reddi2, 3, Steven Piantadosi2, Mario A. Eisenberger2
& Jonathan W. Simons1
1James Buchanan Brady Urological Institute, Marburg 1, the Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, Maryland 21287-2411, USA
2Johns Hopkins Oncology Center, the Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
3Department of Orthopedic Surgery, the Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
4Correspondence should be addressed to J.B.N. Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone−refractory disease is characterized by painful osteoblastic bone metastases. Endothelin−1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin−1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin−1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ectopic endothelin−1 may be a mediator of the osteoblastic response of bone to metastatic prostate cancer.
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