Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells

Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-11, Vol.66 (21), p.10357-10364
Main Authors: YANG, Eric V, SOOD, Anil K, LEMESHOW, Stanley, GLASER, Ronald, MIN CHEN, YANG LI, EUBANK, Tim D, MARSH, Clay B, JEWELL, Scott, FLAVAHAN, Nicholas A, MORRISON, Carl, YEH, Peir-En
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Biopsy
Cell Line, Tumor
Gene Expression Regulation, Neoplastic - drug effects
Humans
Matrix Metalloproteinase 14 - genetics
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 9 - genetics
Medical sciences
Nasopharyngeal Neoplasms - metabolism
Nasopharyngeal Neoplasms - pathology
Neoplasm Invasiveness
Norepinephrine - pharmacology
Otorhinolaryngology. Stomatology
Pharmacology. Drug treatments
Receptors, Adrenergic, beta - physiology
Tumors
Up-Regulation
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
Vascular Endothelial Growth Factor A - genetics
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Summary:Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study is to determine if the stress hormone norepi can influence the expression of MMP-2, MMP-9, and VEGF in nasopharyngeal carcinoma (NPC) tumors by using three NPC tumor cell lines. The NPC cell lines HONE-1, HNE-1, and CNE-1 were treated with norepi. The effects of norepi on MMP-2, MMP-9, and VEGF synthesis were measured by ELISA; functional MMP activity was measured by the invasive potential of the cells using a membrane invasion culture system whereas functional activity of VEGF was analyzed using a human umbilical vein endothelial cell tube formation assay. Norepi treatment increased MMP-2, MMP-9, and VEGF levels in culture supernatants of HONE-1 cells, which could be inhibited by the beta-blocker propranolol. Norepi induced the invasiveness of all NPC cell lines in a dose-dependent manner, which was blocked by CMT-3, an MMP inhibitor, and propranolol. Norepi stimulated the release of functional angiogenic VEGF by HONE-1 cells as well. Finally, HONE-1 cells were shown to express beta-adrenergic receptors as did seven of seven NPC biopsies examined. The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-06-2496