This Article Full Text Full Text (PDF) All Versions of this Article: 90/2/1012    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carpenter, T. O. Articles by Shimkets, R. Search for Related Content PubMed PubMed Citation Articles by Carpenter, T. O. Articles by Shimkets, R. Related Collections Calcium and Bone Metabolism Endocrine Oncology

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

Endocrine Sections of the Departments of Pediatrics (T.O.C., B.K.E.) and Internal Medicine (K.L.I., W.M.P., J.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and CuraGen Corp. (R.S.), New Haven, Connecticut 06511

Address all correspondence and requests for reprints to: Dr. Thomas O. Carpenter, Department of Pediatrics, Yale University School of Medicine, P.O. Box 208064, New Haven, Connecticut 06520-8064. E-mail: thomas.carpenter{at}yale.edu.

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

This article has been cited by other articles:

				S. Liu and L. D. Quarles How Fibroblast Growth Factor 23 Works J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1637 - 1647. [Abstract] [Full Text] [PDF]

				E. A. Imel, M. Peacock, P. Pitukcheewanont, H. J. Heller, L. M. Ward, D. Shulman, M. Kassem, P. Rackoff, M. Zimering, A. Dalkin, et al. Sensitivity of Fibroblast Growth Factor 23 Measurements in Tumor-Induced Osteomalacia J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2055 - 2061. [Abstract] [Full Text] [PDF]

				E. A. Imel and M. J. Econs Fibroblast Growth Factor 23: Roles in Health and Disease J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2565 - 2575. [Full Text] [PDF]

				T. Berndt and R. Kumar The Phosphatonins and the Regulation of Phosphorus Homeostasis IBMS BoneKEy, June 1, 2005; 2(6): 5 - 16. [Full Text] [PDF]

				E. Seeman and G. J. Strewler Clinical and Basic Research Papers - February 2005 Selections IBMS BoneKEy, March 1, 2005; 2(3): 1 - 5. [Full Text] [PDF]