Disease relevance of SFRP2

• SFRP2 methylation is a sensitive single DNA-based marker for the fecal screening of colorectal cancer [1].
• Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli [2].
• The expression and dysregulation of sFRP-2 in fat and obesity also suggest a potential roles on the Wnt signaling pathway in the pathology of obesity and related metabolic diseases [3].
• These findings reveal the key role played by Sfrp2 in mediating the paracrine effects of Akt-mesenchymal stem cells on tissue repair and identify modulation of Wnt signaling as a therapeutic target for heart disease [4].
• The downregulation of sFRP2, 4 and 5 was more frequent in carcinoma than in adenoma [5].

High impact information on SFRP2

• Using a comprehensive functional genomic strategy, we show that secreted frizzled related protein 2 (Sfrp2) is the key stem cell paracrine factor that mediates myocardial survival and repair after ischemic injury [4].
• Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 [6].
• Thus, in addition to enhanced osteolysis, MM cells also suppress bone formation at least in part through an inhibition of the canonical Wnt pathway by secreting sFRP-2 [6].
• The human SFRP5 gene consists of three coding exons and it maps to chromosome 10q24.1; human SFRP2 maps to 4q31 [7].
• In the chick, the premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the cells differentiate, suggesting that Wnts might regulate myogenic differentiation [8].

Biological context of SFRP2

• SFRP1 methylation occurred in all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples [9].
• On the other hand, SFRP2 is claimed to induce cellular resistance to apoptosis in mammary tumors [1].
• Comparative genomics on SFRP2 orthologs [1].
• GC content of human SFRP2 promoter was 63.9% [1].
• SFRP2 gene at human chromosome 4q31.3 is claimed as a tumor suppressor gene inactivated by the epigenetic CpG hypermethylation in colorectal cancer [1].

Anatomical context of SFRP2

• 3. Based on the biology and complementary expression patterns of SFRP2 and SFRP5, we suggest that they may be involved in determining the polarity of photoreceptor, and perhaps other, cells in the retina [7].
• Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm [10].
• Thus, to elucidate the role of SFRP2 in mammary tumorigenesis, we overexpressed SFRP2 in mammary gland tumor and MCF7 cells [11].
• Moreover, SFRP2 was found to induce tumorous transformation in normal mammary epithelial cells and to inhibit apoptosis in a modified paracrine model [11].
• SARP1 and/or SARP2 (92-95 kDa) are ubiquitously expressed in all tissues with high levels in testis and sperm, where they are shown to interact with both PP1gamma1 and PP1gamma2 [12].

Associations of SFRP2 with chemical compounds

• Further, estrogen-induced inhibition of adenogenesis may be mediated by a reduction in WNT signaling caused by aberrant induction of SFRP2 and loss of several critical WNTs [13].
• The cysteine-rich domain of sFRP-2 binds to Wnt-4 as shown by coimmunoprecipitation experiments [14].
• Wnt-4 acts in an autocrine loop to stimulate its own synthesis and is required for cells to differentiate into epithelia; its action is antagonized by sFRP-1, secreted by stroma, but this antagonism is itself inhibited by sFRP-2 made by the developing nephron [15].
• Of those agents tested, TAM appears to be the most and Sarp A the least effective [16].

Regulatory relationships of SFRP2

• We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a [10].
• In contrast, genes encoding SARP1 and various cell cycle regulators were down-regulated in the RA synovium relative to OA [17].

Other interactions of SFRP2

• Expression of SFRP2 and SFRP4 proteins was lower in cancers with corresponding gene methylation (p < 0.05) [18].
• The results indicated that SFRP2 is secreted and incorporated into the extracellular matrix (ECM) of the tumor and normal cells [11].
• SARP3 (65 kDa) is most abundant in brain where SARP isoforms interact with both PP1alpha and PP1gamma1 [12].
• In the present paper we report the cloning and characterization of a new protein, termed SARP (several ankyrin repeat protein), which is shown to interact with all isoforms of PP1 by a variety of techniques [12].
• DKK 1, 3, and 4 as well as sFRP 1, 4, and 5 were expressed in the exocrine fraction. sFRP 2 and 3 were detectable but only at low levels [19].

Analytical, diagnostic and therapeutic context of SFRP2

• In an attempt to understand the molecular basis underlying the interaction between SFRP2 and ECM, co-immunoprecipitation and cell adhesion assays were carried out [11].
• The localization of SFRP2 mRNA by in situ hybridization varied according to the degree of degeneration, from stratified in relatively well-preserved retinas to diffuse in the highly degenerative state [20].
• By Northern blot analysis, SFRP2 mRNA levels were 2- to 20-fold higher in RP samples than in controls [20].
• By immunofluorescence, SFRP2 protein in RP retinas was found mainly to colocalize with the cell adhesion and signal transducing protein beta-catenin [20].
• By RT-PCR and in situ hybridization, SFRP2 gene was found abundantly expressed in neoplastic mammary tissues but not in normal mammary tissues, suggesting that SFRP2 may contribute as a tumor marker in canine MGTs [21].

References