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The development of epithelial-messenchimal transition (EMT) requires alterations in morphology, cellular architecture, adhesion and migration capacity (1).The occurrence of EMT during tumour progression allows tumour cells to acquire the capacity to infiltrate surrounding tissue and metastatize to distant sites.Several soluble growth factors have been demonstrated to induce EMT, i.e.epidermal growth factor (EGF) acting through the HER family of receptors.The vasoactive intestinal peptide (VIP), induces HER-2 transactivation through the PKA-dependent pathway in the human prostate cancer cell line PC3 (2), but its effect on EMT is presently unknown.We have used the human prostate non-tumoral epithelial cell line, RWPE-1 in order to study the effects of VIP on EMT.The results indicate that this neuropeptide promotes changes in morphology: the cells adquire an elongated shape after 24 h treatment with VIP, as detected by immunofluorescence microscopy.Incubation with the peptide for different times increased the expression and secretion of metalloproteases MMP-2 and MMP-9, as measured by RT-PCR and gelatin zymography.VIP decreased cell adhesion and E-cadherin expression in a time dependent fashion.Both the increase of MMPs and the lost of E-eadherin could result in the transformation from the normal epitheloid morphology toward an invasive and less differentiated mesenchymal phenotype.These results suggest that the previously described role of VIP as a pro-metastatic factor at the prostatic level (3) may be initiated by EMT which opens new insights in the search of therapeutical targets for prostate cancer.