Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent

Berndt, Theresa J.; Craig, Theodore A.; Bowe, Ann E.; Vassiliadis, John; Reczek, David; Finnegan, Richard B.; Beur, Suzanne M. Jan de; Schiavi, Susan C.; Kumar, Rajiv

doi:10.1172/jci18563

Cited by 265 publications

(88 citation statements)

References 83 publications

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“…Similar to FGF-23 and ASARM, soluble FRP-4 (sFRP-4) is thought to act as a phosphatonin by reducing the efficiency of renal P i reabsorption and suppressing the synthesis of 1a,25-dihdyroxyvitamin D. 67,68 Recently, sFRP-4 was shown to increase renal P i excretion by reducing NaPi-IIa transporter abundance in the brush border of the proximal tubule through enhanced internalization of the protein. 67 Moreover, sFRP-4 also acts as a minhibin to directly affect bone mineralization.…”

Section: Secreted Frp-4: Phosphatonin or Minhibin?mentioning

confidence: 99%

Recent advances in the renal–skeletal–gut axis that controls phosphate homeostasis

Kiela

Ghishan

2009

Laboratory Investigation

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Under physiological conditions, homeostasis of inorganic phosphate (Pi) is tightly controlled by a network of increasingly more complex interactions and direct or indirect feedback loops among classical players, such as vitamin D (1,25(OH)2D3), parathyroid hormone (PTH), intestinal and renal phosphate transporters, and the recently described phosphatonins and minhibins. A series of checks and balances offsets the effects of 1,25(OH)2D3 and PTH to enable fine-tuning of intestinal and renal Pi absorptive capacity and bone resorption and mineralization. The latter include PHEX, FGF-23, MEPE, DMP1, and secreted FRP4. Despite this large number of regulatory components with complex interactions, the system has limited redundancy and is prone to dysregulation under pathophysiological conditions. This article reviews and synthesizes recent advances to present a new model of Pi homeostasis.

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Section: Secreted Frp-4: Phosphatonin or Minhibin?mentioning

confidence: 99%

Recent advances in the renal–skeletal–gut axis that controls phosphate homeostasis

Kiela

Ghishan

2009

Laboratory Investigation

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“…The pathogenic tumor secretes so-called phosphatonins [3], such as fibroblast growth factor 23 (FGF23) [4], frizzled related protein-4 [5], matrix extracellular phosphoglycoprotein [6] and FGF7 [7], which causes reduced reabsorption of phosphate in the proximal renal tubule. To date, FGF23 is thought to be the primary clinically relevant phosphatonin [8].…”

Section: Introductionmentioning

confidence: 99%

Surgical treatment of tumor-induced osteomalacia: a retrospective review of 40 cases with extremity tumors

Sun

Jin

Qiu

et al. 2015

BMC Musculoskelet Disord

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BackgroundTumor-induced osteomalacia (TIO) is a rare syndrome typically caused by mesenchymal tumors. It has been shown that complete tumor resection may be curative. However, to our knowledge, there has been no report of a large cohort to exam different surgical approaches. This study was aimed to assess outcomes of different surgical options of patients with tumor-induced osteomalacia at a single institution.MethodsPatients with extremity tumors treated in our hospital from January, 2004 to July, 2012 were identified. The minimum follow-up period was 12 months. Patient’s demography, tumor location, preoperative preparation, type of surgeries were summarized, and clinical outcomes were recorded. Successful treatment was defined as significant symptom improvement, normal serum phosphorus and significant improvement or normalization of bone mineral density at the last follow-up. Differences between patients with soft tissue tumors and bone tumors were compared.ResultsThere were 40 (24 male and 16 female) patients identified, with an average age of 44 years. The tumors were isolated in either soft tissue (25 patients) or bone (12 patients) and combined soft tissue and bone invasion was observed in 3 patients. For the primary surgery, tumor resection and tumor curettage were performed. After initial surgical treatment, six patients then received a second surgery. Four patients were found to have malignant tumors base on histopathology. With a minimum follow-up period of 12 months, 80% of patients (32/40) were treated successfully, including 50% of patients (2/4) with malignant tumors. Compared to patients with bone tumor, surgical results were better in patient with soft tissue tumor.ConclusionsSurgical treatment was an effective way for TIO. Other than tumor curettage surgery, tumor resection is the preferred options for these tumors.

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“…These include secreted frizzled-related protein 4, matrix extracellular phosphoglycoprotein and FGF7 [29,30,31]. However, none of these humoral factors have been shown to be elevated in patients with TIO.…”

Section: Tiomentioning

confidence: 99%

Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia

Fukumoto

2014

Endocrinol Metab

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Fibroblast growth factor 23 (FGF23) is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO) is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.

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Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent

Cited by 265 publications

References 83 publications

Recent advances in the renal–skeletal–gut axis that controls phosphate homeostasis

Recent advances in the renal–skeletal–gut axis that controls phosphate homeostasis

Surgical treatment of tumor-induced osteomalacia: a retrospective review of 40 cases with extremity tumors

Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia

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