Circulating epinephrine is not required for chronic stress to enhance metastasis

Abstract

Signaling through β-adrenergic receptors drives cancer progression and β-blockers are being evaluated as a novel therapeutic strategy to prevent metastasis. Orthotopic mouse models of breast cancer show that β-adrenergic signaling induced by chronic stress accelerates metastasis, and that β2-adrenergic receptors on tumor cells are critical for this. Endogenous catecholamines are released during chronic stress: norepinephrine from the adrenal medulla and sympathetic nerves, and epinephrine from the adrenal medulla. β2-adrenergic receptors are much more sensitive to epinephrine than to norepinephrine. To determine if epinephrine is necessary in the effects of stress on cancer progression, we u..