Disease relevance of Frzb

• Together, these data suggest that Frzb/sFRP3 and DN-LRP5 exhibit antitumor activity through the reversal of epithelial-to-mesenchymal transition and inhibition of MMP activities in a subset of prostate cancer [1].
• Here, we report that the Wnt family of embryonic differentiation genes modulate growth of malignant glioma cells in vitro and in vivo and inhibit cellular migration in vitro. sFRPs (soluble Frizzled-related proteins) are soluble proteins that bind to Wnt and interfere with Wnt signaling [2].

High impact information on Frzb

• Oligonucleotides for the 19 Wnt, 10 frizzled receptors genes, and secreted Frizzled-related protein-1 (sFRP or Fzb) were synthesized based on the available sequences [3].
• Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution [4].
• In vitro application of Wnt7a protein or inhibitors of Wnt signaling, secreted Frizzled-related protein 1 or Wnt inhibitory factor 1, disrupts bundle orientation [5].
• This phenotype is nearly identical to the effect of injection of either frzb or dominant negative Xwnt-8 [6].
• Among those examined only Frzb1 was found to be expressed in the presomitic mesoderm and newly formed somites and thus its possible role in regulating myogenesis was investigated in detail [7].

Biological context of Frzb

• Expression pattern of two Frizzled-related genes, Frzb-1 and Sfrp-1, during mouse embryogenesis suggests a role for modulating action of Wnt family members [8].
• Transplacental delivery of the Wnt antagonist Frzb1 inhibits development of caudal paraxial mesoderm and skeletal myogenesis in mouse embryos [7].
• Inhibition of myogenesis did not appear to be associated with increased cell death since the final number of cells in the explants grown in the presence of Frzb1 was only slightly reduced in comparison with controls [7].
• In order to examine the possible function of Frzb1 in vivo, we developed a method based on the overexpression of the soluble antagonist by transient transfection of WOP cells with a Frzb1 expression vector and injection of transfected cells into the placenta of pregnant females before the onset of maternofoetal circulation [7].
• The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice [9].

Anatomical context of Frzb

• We conclude from these experiments that Frzb-1 is expressed at a time and location to modulate the action of Wnt family members during development of the limbs and central nervous system [8].
• Sexually dimorphic expression of secreted frizzled-related (SFRP) genes in the developing mouse Müllerian duct [10].
• To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation [11].
• Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation [12].
• MATERIALS AND METHODS: We examined the effects of mouse recombinant sFRP3 and/or Wnt-3A on cell proliferation and differentiation using MC3T3-E1 mouse osteoblasts and primary cultures of mouse bone marrow stromal cells [11].

Regulatory relationships of Frzb

• Based on our findings, we propose that sFRP3 may stimulate differentiation through a beta-catenin-independent pathway in addition to its previously known function as a decoy receptor for Wnt's [11].

Other interactions of Frzb

• Developmental expression patterns of mouse sFRP genes encoding members of the secreted frizzled related protein family [13].
• We evaluated the effects of sFRP3 on beta-catenin levels using Western immunoblot analyses [11].
• Evaluation of mouse Sfrp3/Frzb1 as a candidate for the lst, Ul, and Far mutants on chromosome 2 [14].
• FDD-PCR and sequence analysis revealed that the faciogenital dysplasia gene (Rho member families) and secreted frizzled related protein 1 (modulator of Wnt networks) were enhanced only in the Group A-30 [15].

References