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Details

Autor(en) / Beteiligte
Titel
Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction
Ist Teil von
  • Cancer research (Chicago, Ill.), 2018-06, Vol.78 (12), p.3233-3242
Ort / Verlag
United States: American Association for Cancer Research, Inc
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
Beschreibungen/Notizen
  • 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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