The neuroendocrine impact of chronic stress on cancer

Cell Cycle. 2007 Feb 15;6(4):430-3. doi: 10.4161/cc.6.4.3829. Epub 2007 Feb 9.

Abstract

Behavioral processes have long been suspected to influence many health processes including effects on cancer. However, mechanisms underlying these observations are not fully understood. Recent work has demonstrated that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden, and a more invasive pattern of ovarian cancer growth in an orthotopic mouse model. These effects are mediated primarily through the beta(2) adrenergic receptor (ADRB2) activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway. Additionally, tumors in stressed animals have increased vascularization and enhanced expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) -2 and -9. In this review, we highlight the importance of the neuroendocrine stress response in tumor biology and discuss mechanisms by which the beta-adrenergic receptors on ovarian cancer cells enhance angiogenesis and tumor growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma / blood supply
  • Carcinoma / etiology*
  • Carcinoma / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Neovascularization, Pathologic
  • Neurosecretory Systems / metabolism*
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / metabolism
  • Receptors, Adrenergic, beta-2 / physiology*
  • Signal Transduction
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Receptors, Adrenergic, beta-2
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Cyclic AMP-Dependent Protein Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse