Journal
PSYCHONEUROENDOCRINOLOGY
Volume 51, Issue -, Pages 262-270Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2014.10.004
Keywords
Restraint stress; Sympathetic nervous system; Catecholamines; alpha-Adrenergic receptor; Breast cancer; Metastasis; Bioluminescent imaging
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Funding
- NCI [R01CA160890, P30CA016042]
- National Breast Cancer Foundation (Australia) [ECR-11-11]
- UCLA Cousins Center for Psychoneuroimmunology
- NATIONAL CANCER INSTITUTE [P30CA016042, R01CA160890] Funding Source: NIH RePORTER
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Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of beta-adrenergic receptors. Catecholamines also signal alpha-adrenergic receptors, and greater alpha-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of alpha-adrenergic receptors can result in elevated catecholamine levels, which may increase beta-adrenergic signaling, because pre-synaptic alpha(2)-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of alpha-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231 HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective alpha-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective beta-blocker propranolol inhibited the effect of phentolarnine on breast cancer progression. Selective alpha(2)-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective alpha(1)-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that alpha(2)-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of beta-adrenergic signaling on tumor progression-relevant biology. (C) 2014 Elsevier Ltd. All rights reserved.
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