Identification and cloning of a secreted protein related to the cysteine-rich domain of frizzled. Evidence for a role in endothelial cell growth control.

We report the isolation of a cDNA, FrzA (frizzled in aorta; GenBank accession No. U85945), from bovine aortic endothelium. It is the bovine counterpart of the mouse sFRP1, which encodes for a secreted protein that is homologous to the cysteine-rich domain of frizzled. Members of the frizzled family of genes have been shown to be required for tissue polarity and to act as receptors for Wnt. The predicted protein product of this gene includes the cysteine-rich extracellular domain, but not the 7 putative transmembrane domains that are highly conserved among members of the frizzled family. Visualization of FrzA mRNA and protein revealed that it was widely distributed among adult tissues. FrzA is expressed by highly differentiated or polarized cells, eg, neurons, cardiocytes, or various epithelia. Analysis of its expression in endothelium revealed that FrzA mRNA levels were high in endothelial cells scraped from freshly obtained bovine aortas, decreased when cells were placed in culture and began to proliferate, but increased at confluence. Transient transfection assays and an assay using addition of purified protein indicate that FrzA reduces the proliferation of endothelial cells. These data demonstrate the existence of a secreted protein homologous to the extracellular domain of the fz receptor, which we speculate plays a role in controlling cell growth and differentiation, possibly by regulating accessibility to Wnt family members.