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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
Open accessAbstract
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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“It is known within the cancer literature that stress levels of NE increase MMP-9 and MMP-2 that increase invasive potential of the tumor cells (Sood et al, 2006;Yang et al, 2006).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Yang et al, 2006
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Self-citationSympathetic nervous system regulation of the tumour microenvironment
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Metadata
- 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,
- Venue
- Cancer Research
- Published
- 2006-11-01
- Volume
- 66
- Issue
- 21
- Pages
- 10357-10364
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- 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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