VEGF-C expression in oral cancer by neurotransmitter-induced activation of beta-adrenergic receptors.
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.
Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, 17012-901, Bauru, São Paulo, Brazil.
Bruna Maria Rodrigues
BM
Vilardi
Diego Mauricio
DM
Bravo-Calderón
Daniel Galera
DG
Bernabé
Sandra Helena Penha
SH
Oliveira
Denise Tostes
DT
Oliveira
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D018377:Neurotransmitter Agents; D011943:Receptors, Adrenergic, beta; D042582:Vascular Endothelial Growth Factor C; D011433:Propranolol; D009638:Norepinephrine