title: Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model.
abstract: OBJECTIVE
  Chronic stress was previously reported to play a role in the development of oral cancer, yet the correlation between stressors and oral cancer progression is not well understood.
  
  
  METHODS
  We implanted human oral cancer cell line CAL 27 in nude mice to investigate the effects of chronic stress on tumor growth, and designed a physical restraint system to create an experimentally stressed animal model, in which periodic immobilization induced characteristic chronic stress. Tumor burdened animal were randomly assigned into four groups: (a) control group, (b) daily stress for 2h with light, (c) daily stress for 2h in dark, and (d) daily stress for 6h with light. Animals were sacrificed after three weeks. Various analyses were performed on parameters including body weight, tumor weight, in situ expression of MMP-2 and VEGF, and the plasma concentrations of epinephrine, norepinephrine and glucocorticoid.
  
  
  CONCLUSIONS
  Our data showed that chronic stress resulted in greater tumor size, more expression of MMP-2 and VEGF, higher level of plasma catecholamines, and more invasive growth of oral carcinoma cells in a mice model. We have successfully set up an animal model, which studied the effect of chronic stress on oral carcinoma growth rate and progression. These data further suggested that catecholamine and glucocorticoid might stimulate tumor progression under chronic stress.
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia.
authors: Huixu
authors: H
authors: Xie
authors: Medical Scientific Academy in Sichuan People's Hospital, Chengdu, Sichuan 610031, China.
authors: Chuansong
authors: C
authors: Li
authors: College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia.
authors: Yan
authors: Y
authors: He
authors: College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia.
authors: Robert
authors: R
authors: Griffin
authors: College of Medicine and Dentistry, James Cook University, Cairns, QLD 4878, Australia. Electronic address: qingsongye@hotmail.com.
authors: Qingsong
authors: Q
authors: Ye
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: muzili63@163.com.
authors: Longjiang
authors: L
authors: Li
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004837:Epinephrine / Q000097:blood; D005938:Glucocorticoids / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D013315:Stress, Psychological / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D009638:Norepinephrine; D004837:Epinephrine
keywords: Animal model; Catecholamine; Chronic stress; Oral cancer