Cited by 407Cancer, Stress, Anesthesia, and Immune ResponseProtease and Inhibitor MechanismsAngiogenesis and VEGF in Cancer

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Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells

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Yang, Eric V., Sood, Anil K., Chen, Min, Li, Yang, Eubank, Tim D., Marsh, Clay B., Jewell, Scott, Flavahan, Nicholas A., Morrison, Carl, Yeh, Peir-En, Lemeshow, Stanley, Glaser, Ronald·2006·Cancer Research

DOI 10.1158/0008-5472.can-06-2496

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Abstract

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 β-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 β-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. (Cancer Res 2006; 66(21): 10357-64)

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Authors: Yang, E. V., Sood, A. K., Chen, M., Li, Y., Eubank, T. D., Marsh, C. B., Jewell, S., Flavahan, N. A., Morrison, C., Yeh, P.-E., Lemeshow, S., & Glaser, R.
Affiliations: Institute for Behavioral Medicine (US)
The University of Texas MD Anderson Cancer Center (US)
4The Dorothy M. Davis Heart and Lung Research Institute, Departments of
The Ohio State University Wexner Medical Center (US)
3Comprehensive Cancer Center,
ORCID: Sood, Anil K.
Chen, Min
Li, Yang
Jewell, Scott
Flavahan, Nicholas A.
Morrison, Carl
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2006-11-01
Volume: 66
Issue: 21
Pages: 10357-10364
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-2496
OpenAlex: W2138150045
Cited by: 407
References: 50
Citations by year: 2026: 9 · 2025: 13 · 2024: 14 · 2023: 14 · 2022: 16 · 2021: 20 · 2020: 22 · 2019: 23 · 2018: 14 · 2017: 15 · 2016: 27 · 2015: 17 · 2014: 24 · 2013: 35 · 2012: 39
FWCI: 9.33
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: Ohio State University (CA16058)
National Heart, Lung, and Blood Institute (R01HL067176, HL067176)
National Cancer Institute (CA100243, CA10929801, CA16058, R01CA100243, CA 11079301, P30CA016058)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: norepinephrine, nasopharyngeal carcinoma, vascular endothelial growth factor, MMP-2, MMP-9, tumor invasion, angiogenesis, beta-adrenergic receptors, propranolol, catecholamines, tumor progression
MeSH terms: Biopsy, Humans, Nasopharyngeal Neoplasms, Neoplasm Invasiveness, Norepinephrine, Receptors, Adrenergic, beta, Up-Regulation, Gene Expression Regulation, Neoplastic, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Matrix Metalloproteinase 14

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Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells

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