Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells

In oncogenic osteomalacia (OOM), a tumor produces an unknown substance that inhibits phosphate reabsorption in the proximal tubules. This causes urina ry phosphate wasting and, as a consequence, hypophosphatemic osteomalacia. To characterize this poorly understood biological tumor activin we generate d aqueous extracts from several OOM tumors. Extracts from three of four tum ors inhibited, dose- and time-dependently, P-32-orthophosphate uptake by op ossum kidney (OK) cells; maximum inhibition was about 45% of untreated cont rol Further characterization revealed that the factor is resistant to heat and several proteases, and that it has a low molecular weight. The tumor ex tracts also stimulated cAMP accumulation in OK cells, but not in osteoblast ic ROS 17/2.8 and UMR106 cells, or in LLC-PK1 kidney cells expressing the p arathyroid 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 inhibit ed P-32 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 abi lity to inhibit phosphate transport in OK cells can he found in extracts fr om OOM tumors. It remains uncertain, however, whether these are related to the long-sought phosphaturic factor responsible for the phosphate wasting s een in OOM patients.