Disease relevance of SFRP4

• Here, we report that silencing of SFRP4 is correlated with promoter hypermethylation in beta-catenin-deficient mesothelioma cell lines [1].
• Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form [2].
• Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas [2].
• Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1alpha, 25-dihydroxyvitamin D [3].
• The sFRP-4 is detectable in normal human serum and in the serum of a patient with tumor-induced osteomalacia [3].

High impact information on SFRP4

• Currently, the best-characterized group of phosphatonin-like polypeptides includes secreted frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor-23 [4].
• In cultured opossum renal epithelial cells, sFRP-4 specifically inhibited sodium-dependent phosphate transport [3].
• We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples [5].
• Conversely, knocking down SFRP4 by small interfering RNA in cell lines expressing both SFRP4 and beta-catenin stimulates Wnt signaling, promotes cell growth, and inhibits chemodrug-induced apoptosis [1].
• Frizzled 4, axin and frpHE did not have a previous chromosomal assignment and were linked by RHM to chromosome markers, SHGC-35131 at 11q22.1, NIB1488 at 16p13.3 and D7S2919 at 7p15.2, respectively [6].

Chemical compound and disease context of SFRP4

• Interestingly, despite the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25-dihydroxyvitamin D (1alpha,25(OH)(2)D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1alpha-hydroxylase activity [7].
• In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r2 = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia [8].

Biological context of SFRP4

• Our results suggest that methylation silencing of SFRP4 may play an important role in aberrant Wnt activation in mesothelioma even in the absence of beta-catenin [1].
• Reexpression of SFRP4 in these beta-catenin-deficient mesothelioma cell lines blocks Wnt signaling, induces apoptosis, and suppresses growth [1].
• The upregulated genes included those involved in cell cycle regulation (CDKN2A), cell differentiation (SFRP4) and DNA repair (RAD51AP1), while the downregulated genes included those involved in proteolysis (PRSS3) [9].
• CONCLUSIONS: These data suggest that sFRP4 expression may be prognostic for localized PC, potentially as a consequence of an inhibitory effect on PC cell proliferation [10].
• Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy [11].

Anatomical context of SFRP4

• Other phosphatonins may exist, such as matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein 4 (SFRP4), whose role remains to be defined [12].
• We conclude that sFRP-4 increases renal P(i) excretion by reducing Na(+)-P(i)-IIa transporter abundance in the brush border of the proximal tubule through enhanced internalization of the protein [13].

Other interactions of SFRP4

• Expression of SFRP2 and SFRP4 proteins was lower in cancers with corresponding gene methylation (p < 0.05) [14].
• In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4-5 days after transplantation [8].

Analytical, diagnostic and therapeutic context of SFRP4

• By in situ hybridization, we have determined that frpHE is expressed by mesenchymal cells but not by epithelial cells [11].

References