α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

Donald M Lamkin, Ha Yeon Sung, Gyu Sik Yang, John M David, Jeffrey C Y Ma, Steve W Cole, Erica K Sloan

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)262-270
Number of pages9
JournalPsychoneuroendocrinology
Volume51
DOIs
Publication statusPublished - 2015

Keywords

  • Bioluminescent imaging
  • Breast cancer
  • Catecholamines
  • Metastasis
  • Restraint stress
  • Sympathetic nervous system
  • α-Adrenergic receptor

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