Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate

Nat Med. 1995 Sep;1(9):944-9. doi: 10.1038/nm0995-944.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / blood supply
  • Adenocarcinoma / physiopathology
  • Adenocarcinoma / secondary*
  • Adult
  • Aged
  • Alkaline Phosphatase / biosynthesis
  • Base Sequence
  • Bone Neoplasms / blood
  • Bone Neoplasms / blood supply
  • Bone Neoplasms / physiopathology
  • Bone Neoplasms / secondary*
  • Endothelins / blood
  • Endothelins / physiology*
  • Enzyme Induction
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ischemia / blood
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / physiology*
  • Osteoblasts / metabolism
  • Pain / etiology
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Tumor Cells, Cultured
  • Vasoconstriction


  • Endothelins
  • Neoplasm Proteins
  • Alkaline Phosphatase