Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model

•Construct a mice model to confirm the effects of chronic stress on oral cancer.•Chronic stress stimulates catecholamine and glucocorticoid expression in oral cancer mice.•The angiogenic effects of catecholamine and glucocorticoid promote oral cancer growth.•This model can be used for studies on the relation of oral cancer and chronic stress.

SummaryObjectivesChronic 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.Materials and methodsWe 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 2 h with light, (c) daily stress for 2 h in dark, and (d) daily stress for 6 h 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.Results and conclusionOur 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.