title: β2-AR-HIF-1α: a novel regulatory axis for stress-induced pancreatic tumor growth and angiogenesis.
abstract: The purpose of this study was to test the hypothesis that chronic stress in a negative social and psychological state plays a critical role in pancreatic cancer development and progression. In this study, we created a new stress model system to determine the effects of chronic stress on pancreatic cancer progression. Here, we show that chronic stress not only causes depression in mice, most likely attributed to an elevated level of epinephrine, but also induces pancreatic cancer progression. We provide evidence that the pancreatic cancer progression induced by chronic stress could be blocked to a significant degree by β2-AR inhibitor ICI118 551 or HIF-1α inhibitor 2-methoxyestradiol. Moreover, establishment of pancreatic cancer in mice exposed to chronic stress was accompanied by up-regulation of the expression of MMP-2, MMP-9, and VEGF, mediated by a HIF- 1α-dependent β-AR signaling pathway. Our data suggest that the β2-AR-HIF-1α axis regulates stress-induced pancreatic tumor growth and angiogenesis. This study may have a therapeutic or preventive potential for the patients with pancreatic cancer who are especially prone to psychosocial stress challenges.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: T
authors.initials: T
authors.lastname: Shan
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Wu
mesh_terms: D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004837:Epinephrine / Q000097:blood; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics / Q000473:pathology*; D009929:Organ Size; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004837:Epinephrine