Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells.
Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells.
复制标题
引起致癌性骨软化症的肿瘤提取物会抑制负鼠肾细胞对磷酸盐的吸收。
作者：
K. Jonsson;M. Mannstadt;A. Miyauchi;Im;G. Stein;Ö. Ljunggren;H. Jüppner
在致癌性骨软化症 (OOM) 中，肿瘤会产生一种未知物质，抑制近端肾小管的磷酸盐重吸收。这会导致尿磷浪费，从而导致低磷血症性骨软化症。为了表征这种人们知之甚少的生物肿瘤活性，我们从几种 OOM 肿瘤中提取了水提取物。四种肿瘤中的三种提取物可剂量和时间依赖性地抑制负鼠肾 (OK) 细胞对 (32)P-正磷酸盐的摄取；最大抑制约为未处理对照的45%。进一步的表征表明，该因子耐热和多种蛋白酶，并且具有低分子量。肿瘤提取物还刺激 OK 细胞中的 cAMP 积累，但不刺激成骨细胞 ROS 17/2.8 和 UMR106 细胞，或表达甲状旁腺激素 (PTH)/PTH 相关肽受体或 PTH-2 受体的 LLC-PK1 肾细胞。肿瘤提取物的低分子量级分的 HPLC 分离表明，所有三种阳性肿瘤提取物的流过均抑制 (32)P 摄取并刺激 OK 细胞中 cAMP 的积累。此外，在最有效的肿瘤提取物中还发现了第二个峰，对磷酸盐转运具有抑制活性，但没有 cAMP 刺激活性。我们得出的结论是，在 OOM 肿瘤的提取物中可以发现几种能够抑制 OK 细胞中磷酸盐转运的低分子量分子。然而，目前尚不确定这些是否与长期寻找的导致 OOM 患者磷酸盐消耗的磷酸盐因子有关。
In oncogenic osteomalacia (OOM), a tumor produces an unknown substance that inhibits phosphate reabsorption in the proximal tubules. This causes urinary phosphate wasting and, as a consequence, hypophosphatemic osteomalacia. To characterize this poorly understood biological tumor activity we generated aqueous extracts from several OOM tumors. Extracts from three of four tumors inhibited, dose- and time-dependently, (32)P-orthophosphate uptake by opossum kidney (OK) cells; maximum inhibition was about 45% of untreated control. Further characterization revealed that the factor is resistant to heat and several proteases, and that it has a low molecular weight. The tumor extracts also stimulated cAMP accumulation in OK cells, but not in osteoblastic ROS 17/2.8 and UMR106 cells, or in LLC-PK1 kidney cells expressing the parathyroid hormone (PTH)/PTH-related peptide receptor or the PTH-2 receptor. HPLC separation of low molecular weight fractions of the tumor extracts revealed that the flow-through of all three positive tumor extracts inhibited (32)P uptake and stimulated cAMP accumulation in OK cells. Additionally, a second peak with inhibitory activity on phosphate transport, but without cAMP stimulatory activity, was identified in the most potent tumor extract. We have concluded that several low molecular weight molecules with the ability to inhibit phosphate transport in OK cells can be found in extracts from OOM tumors. It remains uncertain, however, whether these are related to the long-sought phosphaturic factor responsible for the phosphate wasting seen in OOM patients.
甲状旁腺激素相关肽 (1-36) 类似物 N 末端区域的研究：受体亚型选择性激动剂、拮抗剂和光化学交联剂。
DOI：
10.1210/endo.140.11.7102
发表时间：
1999
期刊：
Endocrinology.
影响因子：
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作者：
Carter,PH;Juppner,H;Gardella,TJ
通讯作者：
Gardella,TJ