title: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.
abstract: Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.
authors.affiliation: Department of Gynecologic Oncology, University of Texas (U.T.) M.D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, Texas 77030, USA.
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.forename: Liz Y
authors.initials: LY
authors.lastname: Han
authors.forename: Aparna A
authors.initials: AA
authors.lastname: Kamat
authors.forename: Jesusa M
authors.initials: JM
authors.lastname: Arevalo
authors.forename: Rie
authors.initials: R
authors.lastname: Takahashi
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Jennings
authors.forename: Guillermo
authors.initials: G
authors.lastname: Armaiz-Pena
authors.forename: James A
authors.initials: JA
authors.lastname: Bankson
authors.forename: Murali
authors.initials: M
authors.lastname: Ravoori
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Lin
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Kim
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: Charles N
authors.initials: CN
authors.lastname: Landen
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Edward
authors.initials: E
authors.lastname: Felix
authors.forename: Angela M
authors.initials: AM
authors.lastname: Sanguino
authors.forename: Robert A
authors.initials: RA
authors.lastname: Newman
authors.forename: Mary
authors.initials: M
authors.lastname: Lloyd
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000819:agonists; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009929:Organ Size; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D010793:Phthalazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011859:Radiography; D011897:Random Allocation; D013315:Stress, Psychological; D013726:Terbutaline / Q000819:agonists; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D010793:Phthalazines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; C404768:vatalanib; D007545:Isoproterenol; D013726:Terbutaline