title: Expression of beta2-adrenergic receptor in oral squamous cell carcinoma.
abstract: 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.
authors.affiliation: Key Laboratory of Oral Biomedical Engineering, Ministry of Education of China, School of Stomatology, Wuhan University, Wuhan, China. shangzhengjun@hotmail.com
authors.forename: Zheng Jun
authors.initials: ZJ
authors.lastname: Shang
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: De Feng
authors.initials: DF
authors.lastname: Liang
mesh_terms: 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
chemical_list: 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