title: Increased plasminogen activator and type IV collagenase activity in invasive follicular thyroid carcinoma cells.
abstract: BACKGROUND
  An essential difference between benign and malignant follicular thyroid tumors is the ability to invade and metastasize. Thyrotropin (TSH) stimulates invasion of cultured human follicular thyroid cancer cells (FTC-133) via a protein kinase C (PKC) dependent mechanism. Tumor invasion depends on degradation of extracellular matrix by proteases.
  
  
  METHODS
  We analyzed protease activity in FTC-133 and its more invasive clone, FTC-238. Cells were treated with TSH or 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a PKC agonist, for 24 hours. Conditioned medium and cellular extract were subjected to substrate gel zymography with either casein-plasminogen or gelatin (collagen). Western blot and immunohistochemistry confirmed protease identity.
  
  
  RESULTS
  We found increased 50 kd urokinase-like plasminogen activator (uPA) and 62 kd gelatinase activity by FTC-238 cells compared with the less invasive FTC-133 cells. There was no effect of TSH on uPA or collagenase activity at concentrations of 0.01 to 10 mU/ml. In both FTC-133 and FTC-238, TPA incubations of 0.1 to 100 ng/ml caused a dose-dependent increase in uPA and a 94 kd type IV collagenase.
  
  
  CONCLUSIONS
  These findings show that TSH-stimulated invasion may be due to PKC-induced activation of uPA and 94 kd type IV collagenase. uPA and basement membrane type IV collagenase warrant investigation as markers for follicular thyroid cancer.
mesh_terms: D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D013972:Thyrotropin; D011493:Protein Kinase C; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D018093:Gelatinases