Increased plasminogen activator and type IV collagenase activity in invasive follicular thyroid carcinoma cells.

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.

Indications for parathyroidectomy and extent of treatment for patients with secondary hyperparathyroidism.

Some manifestations of secondary hyperparathyroidism affect most if not all patients with chronic renal failure and can affect many different organ systems. Proper medical treatment is essential and should be attempted before considering surgical intervention. The symptoms that most often resolve after parathyroidectomy include bone pain and intractable pruritus. Other useful indications for operation include a marked elevation of the parathyroid hormone level and the elevation of the calcium x phosphate product over 70. Both subtotal parathyroidectomy and total parathyroidectomy with autotransplantation have been advocated as the best operative approach. Each of these procedures has its own advantages and disadvantages which should be considered for each individual case. Localizing procedures should be reserved for patients with persistent or recurrent hyperparathyroidism, as diffuse parathyroid hyperplasia is the most common operative finding in secondary hyperparathyroidism.