Expression of beta2-adrenergic receptor in oral squamous cell carcinoma.
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.


CONCLUSIONS
Increased expression of beta(2)-AR may play an important role in the formation and metastasis of OSCC.
Shang
Zheng Jun
ZJ
Key Laboratory of Oral Biomedical Engineering, Ministry of Education of China, School of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@hotmail.com
Liu
Ke
K
Liang
De Feng
DF
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D011433:Propranolol; D009638:Norepinephrine