title: Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines.
abstract: OBJECTIVE
  Stress has long been believed to influence carcinogenesis, but little is known about physiological mechanisms that may underlie these effects. We have recently observed lower levels of vascular endothelial growth factor (VEGF) in ovarian cancer patients with greater social support, whereas higher VEGF was found in patients with greater distress. The goal of this study was to examine possible mechanisms underlying these relationships.
  
  
  METHODS
  The effects of stress-related mediators including norepinephrine (NE), epinephrine, isoproterenol (a nonspecific beta-adrenergic agonist), and cortisol on the production of VEGF by the ovarian cell lines SKOV3 and EG were investigated.
  
  
  RESULTS
  NE and isoproterenol significantly enhanced VEGF production by SKOV3 cells, and all three of the adrenergic agonists enhanced VEGF production by EG cells. These effects were blocked by the beta antagonist propranolol, supporting a role for beta-adrenergic receptors in these effects. Reverse transcriptase-PCR studies indicated constitutive expression of beta-1 and beta-2 adrenergic receptors on both cell lines. Effects of cortisol on VEGF production varied according to the specific cell line and dose, with stimulating effects on SKOV3 at pharmacologic doses (1000 nM) and on EG at physiological stress level doses (10 nM), and inhibitory effects on EG at pharmacologic doses. Although priming with cortisol blunted NE-induced VEGF production from both cell lines at 3 h, significant increases in VEGF were still seen. Priming with cortisol enhanced isoproterenol-induced VEGF production from SKOV3.
  
  
  CONCLUSIONS
  These findings provide the first experimental evidence of a pathway by which biobehavioral stress mediators could directly contribute to the progression of ovarian tumors.
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, Iowa 52242, USA. susan.lutgendorf@uiowa.edu
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.forename: Steven
authors.initials: S
authors.lastname: Cole
authors.forename: Erin
authors.initials: E
authors.lastname: Costanzo
authors.forename: Sarah
authors.initials: S
authors.lastname: Bradley
authors.forename: Jeremy
authors.initials: J
authors.lastname: Coffin
authors.forename: Sarvenaz
authors.initials: S
authors.lastname: Jabbari
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Rainwater
authors.forename: Justine M
authors.initials: JM
authors.lastname: Ritchie
authors.forename: Maria
authors.initials: M
authors.lastname: Yang
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; D007545:Isoproterenol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine