Expression analysis of fibroblast growth factor-23, matrix extracellular phosphoglycoprotein, secreted frizzled-related protein-4, and fibroblast growth factor-7: identification of fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein as major factors involved in tumor-induced osteomalacia.
OBJECTIVE
To evaluate the expression of various phosphaturic factors in the tumor of a patient with tumor-induced osteomalacia (TIO) and to analyze serum levels of fibroblast growth factor (FGF)-23 in TIO and healthy subjects.


METHODS
We measured serum FGF-23 levels in 2 patients with TIO and 6 healthy volunteers. Expression of FGF-23, matrix extracellular phosphoglycoprotein (MEPE), FGF-7, and secreted frizzled-related protein-4 (sFRP-4) was analyzed in a hemangiopericytoma from a patient with TIO, in a hemangiopericytoma from a patient without TIO, and in various control cell lines.


RESULTS
Serum FGF-23 levels were substantially higher in patients with TIO in comparison with those in healthy control subjects and normalized with successful resection of the tumor. Tissue expression analysis showed preferential expression of FGF-23 and MEPE in TIO-related hemangiopericytoma, whereas FGF-7 and sFRP-4 were widely expressed in all studied cell lines and tissues.


CONCLUSIONS
These results support the use of FGF-23 measurements for the diagnosis and follow-up of patients with TIO. In addition, the specific expression of FGF-23 and MEPE in the TIO-associated tumor suggests an important role of these two phosphatonins in the pathogenesis of TIO. Because of the limited number of patients in our report, further studies are needed to clarify the role of different phosphatonins in the development of the clinical features of TIO.
Habra
Mouhammed Amir
MA
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Jimenez
Camilo
C
Huang
Su-Chen Eileen
SC
Cote
Gilbert J
GJ
Murphy
William A
WA
Gagel
Robert F
RF
Hoff
Ana O
AO
D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000150:complications* / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051523:Fibroblast Growth Factor 7 / Q000235:genetics* / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006393:Hemangiopericytoma / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D010018:Osteomalacia / Q000209:etiology / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D016326:Extracellular Matrix Proteins; D051523:Fibroblast Growth Factor 7; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006023:Glycoproteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C000717427:FGF23 protein, human; C496453:FGF7 protein, human; C486579:MEPE protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins