The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo

Int J Oncol. 2015 Aug;47(2):527-34. doi: 10.3892/ijo.2015.3038. Epub 2015 Jun 8.


The metastatic process is the most serious cause of cancer death. Norepinephrine, secreted in chronic stress conditions, stimulates the motility of breast and colon cells through β-adrenergic receptor. On these bases, we examined its possible role in metastasis formation and development in vitro and in vivo. Treatments with norepinephrine (β2-adrenoreceptor agonist) in mice xenografted with human DU145 prostate cancer cells increased the metastatic potential of these cells. Specifically, we showed that treatment of mice with norepinephrine induced a significant increase of the migratory activity of cancer cells in a concentration-dependent manner and that this process was blocked by propanolol (β-adrenergic antagonist). Mice treated with norepinephrine, displayed an increased number of metastatic foci of DU145 cells in inguinal lymph nodes and also showed an increased expression of MMP2 and MMP9 in tumor samples compared to controls. Moreover, we demonstrated that propanolol induced in norepinephrine treated DU145 cells a E-cadherin finger-like membrane protrusions driven by vimentin remodeling. Altogether these data suggest that β2-AR plays an important role in prostate cancer metastasis formation and that the treatment with antagonist propanolol, could represents an interesting tool to control this process in cells overexpressing β2AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • In Vitro Techniques
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Neoplasm Metastasis
  • Norepinephrine / adverse effects*
  • Norepinephrine / pharmacology
  • Propranolol / administration & dosage*
  • Propranolol / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Xenograft Model Antitumor Assays


  • ADRA2B protein, human
  • Adra2b protein, mouse
  • Receptors, Adrenergic, alpha-2
  • Propranolol
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Norepinephrine