The neuroendocrine impact of chronic stress on cancer.
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.
Thaker
Premal H
PH
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
Lutgendorf
Susan K
SK
Sood
Anil K
AK
D000818:Animals; D002277:Carcinoma / Q000098:blood supply / Q000209:etiology* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D009490:Neurosecretory Systems / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000209:etiology* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse