CANDIDATE 56 AND 58 KDA PROTEIN(S) RESPONSIBLE FOR MEDIATING THE RENAL DEFECTS IN ONCOGENIC HYPOPHOSPHATEMIC OSTEOMALACIA

The effects of tumor-conditioned media (TCM) derived from cultured cel ls from an oncogenic hypophosphatemic osteomalacia (OHO) tumor on tran sformed human kidney cells were investigated. Dose-dependent cell deta chment and aggregation occurred in kidney cells cultured in serum-free medium supplemented with TCM, but not in skin fibroblast controls, or in kidney cells cultured in the presence of serum, Kidney cells expos ed to TCM in the presence of serum (0.5%) had reduced Na+-dependent ph osphate cotransport (36%, p < 0.04) acid increased 1 alpha-hydroxylase activity (48%, p < 0.05), In contrast, TCM had no significant effect on Na+-dependent or-methyl-glucose transport, To investigate these eff ects further, serum from an OHO patient, before and after tumor resect ion, was used to raise polyclonal antiserum to tumor-derived products (preoperative and postoperative antiserum, respectively). Changes in N a+-dependent phosphate cotransport and vitamin D metabolism induced by TCM were prevented by the addition of preoperative but not postoperat ive antisera, Furthermore, Western analysis revealed the presence of t wo proteins (similar to 56-58 kDa) in TCM media screened with preopera tive antisera, These proteins were not detected by postoperative antis era and were absent in skin fibroblast control media, Direct inhibitio n of Na+-dependent phosphate cotransport by phosphonoformic acid did n ot affect 1,25-dihydroxy vitamin D, synthesis. These studies provide s upport for a circulating component affecting phosphate handling and vi tamin D metabolism in OHO.