Title |
Sustained adrenergic signaling promotes intratumoral innervation through BDNF induction
|
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Published in |
Cancer Research, June 2018
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DOI | 10.1158/0008-5472.can-16-1701 |
Pubmed ID | |
Authors |
Julie K Allen, Guillermo N Armaiz-Pena, Archana S Nagaraja, Nouara C Sadaoui, Tatiana Ortiz, Robert Dood, Merve Ozcan, Danielle M Herder, Monika Haemmerle, Kshipra M Gharpure, Rajesha Rupaimoole, Rebecca A Previs, Sherry Y Wu, Sunila Pradeep, Xiaoyun Xu, Hee Dong Han, Behrouz Zand, Heather J Dalton, Morgan Taylor, Wei Hu, Justin Bottsford-Miller, Myrthala Moreno-Smith, Yu Kang, Lingegowda S Mangala, Cristian Rodriguez-Aguayo, Vasudha Sehgal, Erika L Spaeth, Prahlad T Ram, Stephen T C Wong, Frank C Marini, Gabriel Lopez-Berestein, Steve W Cole, Susan K Lutgendorf, Mariella De Biasi, Anil K Sood |
Abstract |
Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feedforward loop whereby adrenergic signaling leads to increased tumoral innervation. In response to catecholamines, tumor cells produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK-dependent manner. Elevated BDNF levels in the tumor microenvironment increased innervation by signaling through host neurotrophic receptor tyrosine kinase 2 (TrkB) receptors. In cancer patients, high tumor nerve counts were significantly associated with increased BDNF and norepinephrine levels and decreased overall survival. Collectively, these data describe a novel pathway for tumor innervation with resultant biological and clinical implications. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Portugal | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 37 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 19% |
Researcher | 4 | 11% |
Student > Doctoral Student | 3 | 8% |
Student > Postgraduate | 3 | 8% |
Student > Master | 3 | 8% |
Other | 6 | 16% |
Unknown | 11 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 8 | 22% |
Medicine and Dentistry | 4 | 11% |
Agricultural and Biological Sciences | 4 | 11% |
Immunology and Microbiology | 3 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 2 | 5% |
Unknown | 15 | 41% |