| First Author | Renz BW | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 1 | Pages | 75-90.e7 |
| PubMed ID | 29249692 | Mgi Jnum | J:253745 |
| Mgi Id | MGI:6110644 | Doi | 10.1016/j.ccell.2017.11.007 |
| Citation | Renz BW, et al. (2018) beta2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer. Cancer Cell 33(1):75-90.e7 |
| abstractText | Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras(+/G12D);Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras(+/G12D);LSL-Trp53(+/R172H);Pdx1-Cre (KPC) mice. Therapy with a Trk inhibitor together with gemcitabine also increased survival of KPC mice. Analysis of PDAC patient cohorts revealed a correlation between brain-derived neurotrophic factor (BDNF) expression, nerve density, and increased survival of patients on nonselective beta-blockers. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation. |
