致癌性骨软化症中肿瘤细胞生物活性的特征

Characteristics of tumor cell bioactivity in oncogenic osteomalacia.

作者信息

Nelson A E, Namkung H J, Patava J, Wilkinson M R, Chang A C, Reddel R R, Robinson B G, Mason R S

机构信息

Department of Molecular Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia.

出版信息

Mol Cell Endocrinol. 1996 Nov 29;124(1-2):17-23. doi: 10.1016/s0303-7207(96)03928-7.

DOI:10.1016/s0303-7207(96)03928-7

PMID:9027320

Abstract

Oncogenic osteomalacia is a condition where renal phosphate wasting occurs causing defective mineralisation, in the presence of a tumor. Cultures of cells were established from a hemangiopericytoma resected from a patient with oncogenic osteomalacia. Conditioned media from the cells inhibited phosphate uptake in opossum kidney cells and stimulated of cAMP in rat osteosarcoma cells, a standard parathyroid hormone (PTH)-like assay. This cAMP stimulation was suppressed by the PTH analogue, 3-34 bPTH and also by heat and trypsin treatment of the media. Tests of conditioned media for PTH and parathyroid hormone related protein (PTHrP) immunoreactivity were negative, however, and no hybridisation to probes for PTH, PTHrP or human stanniocalcin was detected in tumor cell RNA on Northern blot. These data support the hypothesis that tumors responsible for oncogenic osteomalacia produce a humoral substance that reduces renal phosphate reabsorption and provide evidence that the factor may act via PTH/PTHrP receptors.

摘要

致癌性骨软化症是一种在存在肿瘤的情况下发生肾性磷酸盐消耗导致矿化缺陷的病症。从一名患有致癌性骨软化症患者切除的血管外皮细胞瘤中建立了细胞培养物。来自这些细胞的条件培养基抑制了负鼠肾细胞对磷酸盐的摄取，并在大鼠骨肉瘤细胞中刺激了环磷酸腺苷（cAMP），这是一种标准的甲状旁腺激素（PTH）样检测。这种cAMP刺激被PTH类似物3-34 bPTH以及对培养基进行加热和胰蛋白酶处理所抑制。然而条件培养基的PTH和甲状旁腺激素相关蛋白（PTHrP）免疫反应性检测为阴性，并且在Northern印迹中肿瘤细胞RNA上未检测到与PTH、PTHrP或人鲽钙蛋白探针的杂交。这些数据支持了以下假设，即导致致癌性骨软化症的肿瘤产生一种体液物质，该物质会减少肾磷酸盐重吸收，并提供证据表明该因子可能通过PTH/PTHrP受体起作用。