The ability of Frzb/secreted Frizzled-related protein 3 (sFRP3) to inhibit Wnt 
signaling and the localization of Frzb/sFRP3 on chromosome 2q to a region 
frequently deleted in cancers have led some investigators to hypothesize that 
Frzb/sFRP3 is a tumor suppressor gene. Here, we examined the biological effects 
of Frzb/sFRP3 on an androgen-independent prostate cancer cell model. We showed 
that expression of Frzb/sFRP3 in PC-3 cells resulted in decreased colony 
formation in soft agar and a dramatic inhibition of tumor growth in a xenograft 
mouse model. When cellular morphology was examined, PC-3 cells expressing 
Frzb/sFRP3 exhibited an increase in cell-cell contact formation accompanied by a 
pronounced induction of epithelial markers E-cadherin and keratin-8 and 
down-regulation of mesenchymal markers N-cadherin, fibronectin, and vimentin. 
This phenomenon suggested a reversal of epithelial-to-mesenchymal transition and 
a less invasive phenotype. Indeed, further in vitro studies with a Matrigel 
assay showed that Frzb/sFRP3 decreased the invasive capacity of PC-3 cells. 
These changes in the biology of PC-3 cells are associated with a decrease in the 
expression and activities of both matrix metalloproteinase (MMP)-2 and MMP-9 as 
well as decreases in AKT activation, cytosolic beta-catenin levels, T-cell 
factor transcription activity, and expression of Slug and Twist. In addition, 
transfection of PC-3 with a dominant-negative low-density lipoprotein 
receptor-related protein 5 (DN-LRP5) coreceptor showed similar biological 
effects as Frzb/sFRP3 transfection. 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.