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.