Background: It has been speculated that chemokines and neurotransmitters might be involved in the organ-specific development of metastases because cancer metastasis is similar to the regulation of migratory activity in leukocytes. Here, we aimed to examine the expression of beta(2)-adrenergic receptor (beta(2)-AR) in oral squamous cell carcinoma (OSCC), and to investigate its correlation with tumor development and metastasis.
Methods: Expression of beta(2)-AR was examined in 65 cases of OSCC specimens, 10 cases of normal oral mucosa, and two cell lines using immunohistochemistry, Western blot and RT-PCR. The differences in beta(2)-AR expression between various groups were evaluated using SPSS 13.0 Statistical Software. Cell proliferation assays were assayed by beta-adrenergic receptors agonists (norepinephrine) and antagonists (propranolol). Norepinephrine-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber.
Results: beta(2)-AR was highly expressed on OSCC compared to normal controls. In OSCC, positive beta(2)-AR expression was significantly correlated with cervical lymph node metastasis (P = 0.001), age (P = 0.003), tumor size (P = 0.001) and clinical stage (P = 0.001), but not with gender. RT-PCR and Western blot also confirmed positive beta(2)-AR expression in OSCC and TCa8113 cell line, and negative beta(2)-AR expression in normal oral mucosa and ACC cell line. beta-adrenoreceptor agonist (norepinephrine) was a potent mitogen for TCa8113 and ACC cell lines, and completely inhibited by the selective antagonist of beta-adrenergic receptors (propranolol). Norepinephrine induced migratory activity of OSCC cells in a dose-dependent manner.
Conclusion: Increased expression of beta(2)-AR may play an important role in the formation and metastasis of OSCC.