Title:β2-AR-HIF-1α: A Novel Regulatory Axis for Stress-Induced Pancreatic Tumor Growth and Angiogenesis
Volume: 13
Issue: 6
Author(s): T. Shan, J. Ma, Q. Ma, K. Guo, J. Guo, X. Li, W. Li, J. Liu, C. Huang, F. Wang and E. Wu
Affiliation:
Keywords:
Angiogenesis, β2-AR, HIF-1α, pancreatic cancer, regulatory axis, stress.
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.