The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels.

Abstract

Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.

• Authors: Akira Ishii, Yasuo Imanishi, Keisuke Kobayashi, Jun Hashimoto, Takafumi Ueda, Akimitsu Miyauchi, Hajime M Koyano, Hiroshi Kaji, Takatoshi Saito, Koichi Oba, Yasato Komatsu, Masafumi Kurajoh, Yuki Nagata, Hitoshi Goto, Kenichi Wakasa, Toshitsugu Sugimoto, Takami Miki, Masaaki Inaba, Yoshiki Nishizawa
• Journal: Calcified tissue international (Calcif Tissue Int) Vol. 86 Issue 6 Pg. 455-62 (Jun 2010) ISSN: 1432-0827 [Electronic] United States
• PMID: 20458578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• FGF23 protein, human
• Phosphates
• Receptors, Somatostatin
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Octreotide

Topics

• Antineoplastic Agents, Hormonal (therapeutic use)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood)
• Gene Expression (drug effects)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Neoplasms (complications, metabolism)
• Octreotide (therapeutic use)
• Osteomalacia (drug therapy, etiology, metabolism)
• Phosphates (blood)
• Receptors, Somatostatin (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction