4.4 Article

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

期刊

CURRENT MOLECULAR MEDICINE
卷 13, 期 6, 页码 1023-1034

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/15665240113139990055

关键词

Angiogenesis; beta 2-AR; HIF-1 alpha; pancreatic cancer; regulatory axis; stress

资金

  1. Major Scientific Grand of Shaanxi [13115 (2010ZDKG-49)]
  2. National Nature Science Foundation of China (NSFC) [81172360, 81201824]
  3. National Center for Research Resources (NCRR), National Institutes of Health (NIH) [P20 RR020151]
  4. National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH) [P20 GM103505 and P30 GM103332-01]

向作者/读者索取更多资源

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 beta 2-AR inhibitor ICI118 551 or HIF-1 alpha 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-1 alpha-dependent beta-AR signaling pathway. Our data suggest that the beta 2-AR-HIF-1 alpha 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.

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