Stern P H, Krieger N S, Nissenson R A, Williams R D, Winkler M E, Derynck R, Strewler G J
J Clin Invest. 1985 Nov;76(5):2016-9. doi: 10.1172/JCI112202.
Tumor-derived transforming growth factors (TGF) have been proposed as possible mediators of hypercalcemia in malignancy. We have studied the action of recombinant human TGF-alpha in cultured bone cells and in bone explant cultures. In clonal UMR-106 rat osteosarcoma cells, TGF-alpha and epidermal growth factor (EGF) were equipotent in binding to the EGF receptor. TGF-alpha and EGF both stimulated resorption of neonatal mouse calvaria, and maximal responses were obtained with 10 ng/ml of TGF-alpha after 72 h in culture. The effects of both TGF-alpha and EGF in calvaria, but not those of parathyroid hormone, were inhibited by 5 X 10(-7) M indomethacin. Fetal rat limb bone cultures were less sensitive to TGF-alpha than neonatal mouse calvaria, with a concentration of 30 ng/ml being required to stimulate resorption in this system. The bone-resorbing activity of TGF-alpha in fetal rat bones was inhibited by 10 ng/ml calcitonin but not by 5 X 10(-7) M indomethacin. EGF at concentrations up to 300 ng/ml did not stimulate resorption of the limb bones at time periods up to 66 h. The results indicate that human TGF-alpha is a potent bone-resorbing agent, and support the concept that this growth factor exhibits some effects distinct from those of EGF. TGF-alpha could play an etiologic role in the hypercalcemia of malignancy.
肿瘤衍生的转化生长因子（TGF）被认为可能是恶性肿瘤中高钙血症的介质。我们研究了重组人TGF-α在培养的骨细胞和骨外植体培养物中的作用。在克隆的UMR-106大鼠骨肉瘤细胞中，TGF-α和表皮生长因子（EGF）与EGF受体的结合能力相当。TGF-α和EGF均刺激新生小鼠颅骨的吸收，培养72小时后，10 ng/ml的TGF-α可获得最大反应。5×10⁻⁷ M的吲哚美辛可抑制TGF-α和EGF对颅骨的作用，但对甲状旁腺激素的作用无抑制作用。胎鼠肢体骨培养物对TGF-α的敏感性低于新生小鼠颅骨，在该系统中刺激吸收需要30 ng/ml的浓度。10 ng/ml的降钙素可抑制TGF-α在胎鼠骨骼中的骨吸收活性，但5×10⁻⁷ M的吲哚美辛无此作用。浓度高达300 ng/ml的EGF在长达66小时的时间段内未刺激肢体骨的吸收。结果表明，人TGF-α是一种有效的骨吸收剂，并支持这种生长因子表现出一些不同于EGF的作用的观点。TGF-α可能在恶性肿瘤高钙血症中起病因学作用。
