Abstract
The aim of this study was to investigate the expression of vascular endothelial growth factor type C (VEGF-C) in oral squamous cell carcinoma (OSCC) cell lines through norepinephrine-induced activation of beta-adrenergic receptors. Human OSCC cell lines (SCC-9 and SCC-25) expressing beta-adrenergic receptors were stimulated with different concentrations of norepinephrine (0.1, 1, and 10 μM) and 1 μM of propranolol, and analyzed after 1, 6, and 24 h. VEGF-C gene expression and VEGF-C production in the cell supernatant were evaluated by real-time PCR and by ELISA, respectively. The results showed that beta-adrenergic receptor stimulation by different concentrations of norepinephrine or blocking by propranolol did not markedly alter VEGF-C expression by SCC-9 and SCC-25 cells. VEGF-C protein levels produced by oral malignant cell lines after stimulation with different norepinephrine concentrations or blocking with propranolol was statistically similar (p > 0.05) to those of the control group (nonstimulated OSCC cell lines). Our findings suggest that stimulation of beta-adrenergic receptors by means of norepinephrine does not seem to modulate the VEGF-C expression in OSCC cell lines. These findings reinforce the need for further studies in order to understand the responsiveness of oral cancer to beta-adrenergic receptor stimulation or blockage, especially with regard to VEGF-C production.
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Acknowledgments
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant nos. 476139/2010-4 and 500991/2010-3) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant no. 2010/06333-3 and FAPESP Pos-doctoral fellowship (DGB) no. 2010/51361-5). The authors thank to Ms. Fátima Aparecida Silveira Camargo for the technical support provided.
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Bruna Maria Rodrigues Vilardi and Daniel Galera Bernabé contributed equally to this work.
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Vilardi, B.M.R., Bravo-Calderón, D.M., Bernabé, D.G. et al. VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors. Tumor Biol. 34, 139–143 (2013). https://doi.org/10.1007/s13277-012-0521-1
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DOI: https://doi.org/10.1007/s13277-012-0521-1