α2-Adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression.
Title | α2-Adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Lamkin DM, Sung HYeon, Yang GSik, David JM, C Y Ma J, Cole SW, Sloan EK |
Journal | Psychoneuroendocrinology |
Volume | 51 |
Pagination | 262-70 |
Date Published | 2015 Jan |
ISSN | 1873-3360 |
Keywords | Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-2 Receptor Antagonists, Animals, Benzofurans, Cell Proliferation, Disease Progression, Female, Imidazoles, Mammary Neoplasms, Experimental, Mice, Neoplasm Metastasis, Prazosin, Restraint, Physical, Signal Transduction, Stress, Physiological, Stress, Psychological |
Abstract | 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 β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-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 β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. |
DOI | 10.1016/j.psyneuen.2014.10.004 |
Alternate Journal | Psychoneuroendocrinology |
PubMed ID | 25462899 |
PubMed Central ID | PMC4406769 |
Grant List | P30 CA016042 / CA / NCI NIH HHS / United States P30CA016042 / CA / NCI NIH HHS / United States R01 CA160890 / CA / NCI NIH HHS / United States R01CA160890 / CA / NCI NIH HHS / United States |