Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction.

Authors:
Julie K Allen
Julie K Allen
University of Texas MD Anderson Cancer Center
United States
Archana S Nagaraja
Archana S Nagaraja
The University of Texas MD Anderson Cancer Center
Houston | United States
Nouara C Sadaoui
Nouara C Sadaoui
The University of Texas MD Anderson Cancer Center
Houston | United States
Tatiana Ortiz
Tatiana Ortiz
College of Medicine
Robert Dood
Robert Dood
The University of Texas MD Anderson Cancer Center
Houston | United States
Danielle M Herder
Danielle M Herder
The University of Texas M.D. Anderson Cancer Center
Houston | United States

Cancer Res 2018 Jun 16;78(12):3233-3242. Epub 2018 Apr 16.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

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 feed-forward 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 receptors. In patients with cancer, 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. Sustained adrenergic signaling promotes tumor growth and metastasis through BDNF-mediated tumoral innervation. .

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Source
http://dx.doi.org/10.1158/0008-5472.CAN-16-1701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004256PMC
June 2018
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