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Epinephrine stimulates secretion of VEGF by human prostate cancer cells, LNCaP, through a beta2‐adrenergic receptor‐mediated pathway
Author(s) -
Bavadekar Supriya,
Budajaja Faten,
Patel Kartik,
Vansal Sandeep
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1105.11
Subject(s) - lncap , angiogenesis , endocrinology , medicine , prostate cancer , epinephrine , secretion , vascular endothelial growth factor , matrix metalloproteinase , receptor , du145 , prostate , cancer research , chemistry , cancer , biology , vegf receptors
Recent research using various cancer models has suggested that β‐adrenergic receptor (AR) activation is associated with increased tumor angiogenesis. Current evidence suggests that these effects may be mediated via the β 2 ‐AR, and involve modulation of the expression of pro‐angiogenic factors such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). The aim of this study was to examine the effects of the AR agonist, epinephrine, on the secretion and/or expression of VEGF, MMP‐2, and MMP‐9 in human metastatic, androgen‐sensitive, functional β 2 ‐AR‐expressing prostate cancer cells, LNCaP, and also to elucidate the molecular mechanism involved. Cells were treated with increasing concentrations (0.1–100 μM) of epinephrine, and levels of secreted VEGF were determined after 24 hr using ELISA. Epinephrine caused a dose‐dependent increase in the level of secreted VEGF. Pretreatment with β‐AR selective antagonists propranolol (10 μM) and ICI 118,551 (10 μM) inhibited the increased VEGF secretion. The data suggest that the effect is mediated predominantly through the β 2 ‐AR pathway, and that blockade of this pathway could have implications for the prevention and treatment of prostate cancer. This work is supported by the Division of Pharmaceutical Sciences at Long Island University and the Touro College of Pharmacy.