Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.
|Title||Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Kim-Fuchs C, Le CP, Pimentel MA, Shackleford D, Ferrari D, Angst E, Hollande F, Sloan EK|
|Journal||Brain Behav Immun|
|Date Published||2014 Aug|
|Keywords||Adrenergic beta-Agonists, Adrenergic beta-Antagonists, Animals, Cell Line, Tumor, Chronic Disease, Cyclic AMP, Disease Progression, Humans, Mice, Mice, Inbred BALB C, Pancreas, Pancreatic Neoplasms, Receptors, Adrenergic, beta, Restraint, Physical, Signal Transduction, Stress, Psychological, Sympathetic Nervous System|
Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.
|Alternate Journal||Brain Behav. Immun.|
|PubMed Central ID||PMC4102665|
|Grant List||CA160890 / CA / NCI NIH HHS / United States |
R01 CA160890 / CA / NCI NIH HHS / United States