as the impact of neural signaling on cancer becomes clearer , it is imperative that stress - sensitive steps in cancer progression are identified for the development of targeted interventions . the findings presented here suggest that targeting either neural or inflammatory signaling activated by stress may limit metastatic dissemination and cancer - related mortality ( fig .  1 ) . this is in line with recent retrospective epidemiologic studies linking -blocker use to improved cancer outcomes . we now demonstrate that -blocker use in cancer patients is linked to reduced tumor cell dissemination to lymph nodes . these findings provide a mechanistic rationale for ongoing clinical trials using -blockers as a possible treatment option for patients with cancer . activation of the sympathetic nervous system increases levels of catecholamines , norepinephrine ( ne ) , and/or epinephrine ( e ) . tumor - associated macrophages respond to ne / e by secreting inflammatory molecules such as prostaglandin e2 ( pge2 ) , which drive the production of vascular endothelial growth factor c ( vegfc ) in tumor cells . various points in this signaling cascade can be targeted using drugs such as -blockers ( bbs ) or non - steroidal anti - inflammatory drugs ( nsaids ) . activation of the sympathetic nervous system increases levels of catecholamines , norepinephrine ( ne ) , and/or epinephrine ( e ) . tumor - associated macrophages respond to ne / e by secreting inflammatory molecules such as prostaglandin e2 ( pge2 ) , which drive the production of vascular endothelial growth factor c ( vegfc ) in tumor cells . various points in this signaling cascade can be targeted using drugs such as -blockers ( bbs ) or non - steroidal anti - inflammatory drugs ( nsaids ) . the research described here was funded by the australian national health and medical research council ( 1008865 and 1053535 ) , the australian research council ( le110100125 ) , the national cancer institute ( ca160890 ) , the australian and new zealand college of anaesthetists ( n13/002 ) , the co - operative research center for cancer therapeutics and the national breast cancer foundation .
abstractchronic stress drives cancer progression , but the routes of metastasis are unclear . 
 we recently demonstrated that chronic stress activates a neural - inflammatory signaling axis to remodel lymphatic vasculature and increase lymph flow . 
 this unanticipated crosstalk between stress and the lymphatic system provides pathways of tumor cell dissemination and accelerates metastasis .