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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

β2-AR-HIF-1α: A Novel Regulatory Axis for Stress-Induced Pancreatic Tumor Growth and Angiogenesis

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

Volume 13, Issue 6, 2013

Page: [1023 - 1034] Pages: 12

DOI: 10.2174/15665240113139990055

Price: $65

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.

Keywords: Angiogenesis, β2-AR, HIF-1α, pancreatic cancer, regulatory axis, stress.


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