Sympathetic nervous system regulation of metastasis

Recent experimental and epidemiologic evidence suggests that systemic physiologic stress-responsive pathways may help shape the tumor microenvironment to promote metastasis. These pathways act through the peripheral sympathetic nervous system to release catecholaminergic neurotransmitters that stimulate signaling through b-adrenergic receptors on tumor cells and tumor-associated macrophages. Experimental studies found that chronic stress accelerated breast cancer metastasis through b-adrenergic signaling pathways that recruit alternatively activated macrophages to primary mammary tumors. Consistent with b-adrenergic regulation of breast cancer, recent clinical studies found that inhibiting b-adrenergic signaling with b-blockers was associated with improved breast-cancer specific outcomes. These and other studies described here suggest that b-blockade of sympathetic nervous system signaling pathways may be a novel adjuvant therapeutic strategy to slow cancer progression and prevent metastasis.