Fibroblast Growth Factor 7: An Inhibitor of Phosphate Transport Derived from Oncogenic Osteomalacia-Causing Tumors

• DOI: 10.1210/jc.2004-0357
• Publication Date: 2005-02-07T20:17:00Z
• Authors: Thomas O. Carpenter; Bruce K. Ellis; Karl L. Insogna; William M. Philbrick; John Sterpka; Richard Shimkets
• Keywords: Adult; Male; 0303 health sciences; Fibroblast Growth Factor 7; Bone Neoplasms; Middle Aged; Fibroblast Growth Factors; Fibroblast Growth Factor-23; Kinetics; 03 medical and health sciences; Gene Expression Regulation; Insulin-Like Growth Factor Binding Protein 4; Cell Line, Tumor; Culture Media, Conditioned; CD4 Antigens; Osteomalacia; Humans; Phosphate Transport Proteins; Child

Oncogenic osteomalacia (OO), a tumor-associated phosphate-wasting syndrome, provides an opportunity to identify regulators of renal phosphate homeostasis. We established cultures from OO-associated tumors. Conditioned medium these inhibited uptake in tubular epithelial cells. then compared RNA tumor-derived expressing inhibitory activity with which was not evident and identified candidate mRNAs specifically expressed by inhibiting transport. Testing candidates revealed that one protein, fibroblast growth factor 7 (FGF7), potent direct inhibitor vitro. A neutralizing monoclonal antibody FGF7 reversed FGF7-dependent transport inhibition conditioned tumor cell cultures. Immunoassay abundant minimal amounts nonconditioned or no activity. Furthermore, only small FGF23 were present medium, comparable concentrations found Thus, when selecting for vitro confirmed as Finally, message PCR products mRNA extracted fragments each tumor. Members the FGF family (other than FGF23) are tumors may play role mediating this syndrome.