Cancer research (Chicago, Ill.), 2018-06, Vol.78 (12), p.3233-3242
- Allen, Julie K
- Armaiz-Pena, Guillermo N
- Nagaraja, Archana S
- Sadaoui, Nouara C
- Ortiz, Tatiana
- Dood, Robert
- Ozcan, Merve
- Herder, Danielle M
- Haemmerle, Monika
- Gharpure, Kshipra M
- Rupaimoole, Rajesha
- Previs, Rebecca A
- Wu, Sherry Y
- Pradeep, Sunila
- Xu, Xiaoyun
- Han, Hee Dong
- Zand, Behrouz
- Dalton, Heather J
- Taylor, Morgan
- Hu, Wei
- Bottsford-Miller, Justin
- Moreno-Smith, Myrthala
- Kang, Yu
- Mangala, Lingegowda S
- Rodriguez-Aguayo, Cristian
- Sehgal, Vasudha
- Spaeth, Erika L
- Ram, Prahlad T
- Wong, Stephen T C
- Marini, Frank C
- Lopez-Berestein, Gabriel
- Cole, Steve W
- Lutgendorf, Susan K
- De Biasi, Mariella
- Sood, Anil K
2018
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- Autor(en) / Beteiligte
- Allen, Julie K
- Armaiz-Pena, Guillermo N
- Nagaraja, Archana S
- Sadaoui, Nouara C
- Ortiz, Tatiana
- Dood, Robert
- Ozcan, Merve
- Herder, Danielle M
- Haemmerle, Monika
- Gharpure, Kshipra M
- Rupaimoole, Rajesha
- Previs, Rebecca A
- Wu, Sherry Y
- Pradeep, Sunila
- Xu, Xiaoyun
- Han, Hee Dong
- Zand, Behrouz
- Dalton, Heather J
- Taylor, Morgan
- Hu, Wei
- Bottsford-Miller, Justin
- Moreno-Smith, Myrthala
- Kang, Yu
- Mangala, Lingegowda S
- Rodriguez-Aguayo, Cristian
- Sehgal, Vasudha
- Spaeth, Erika L
- Ram, Prahlad T
- Wong, Stephen T C
- Marini, Frank C
- Lopez-Berestein, Gabriel
- Cole, Steve W
- Lutgendorf, Susan K
- De Biasi, Mariella
- Sood, Anil K
- 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
- Quelle
- MEDLINE
- 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. .
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.can-16-1701Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6004256
- Format
- –
- Schlagworte
- Animals, Brain tumors, Brain-derived neurotrophic factor, Brain-Derived Neurotrophic Factor - metabolism, Cancer, Catecholamines, Cell Line, Tumor, Cyclic AMP - metabolism, Feedback, Physiological, Female, Guanine Nucleotide Exchange Factors - metabolism, Humans, Innervation, Membrane Glycoproteins - metabolism, Metastases, Metastasis, Mice, Neoplasms - mortality, Neoplasms - pathology, Neurotransmitters, Norepinephrine, Norepinephrine - metabolism, Peripheral Nerves - metabolism, Peripheral Nerves - pathology, Protein-tyrosine kinase receptors, Receptor, trkB - metabolism, Receptors, Adrenergic, beta-3 - metabolism, Signal Transduction, Tumor cells, Tumor Microenvironment - physiology, Xenograft Model Antitumor Assays