Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1.
The carcinogenic potential of vasoactive intestinal peptide (VIP) was analyzed in non-tumor human prostate epithelial cells (RWPE-1) and in vivo xenografts. VIP induced morphological changes and a migratory phenotype consistent with stimulation of expression/activity of metalloproteinases MMP-2 and MMP-9, decreased E-cadherin-mediated cell-cell adhesion, and increased cell motility. VIP increased cyclin D1 expression and cell proliferation that was blocked after VPAC(1)-receptor siRNA transfection. Similar effects were seen in RWPE-1 tumors developed by subcutaneous injection of VIP-treated cells in athymic nude mice. VIP acts as a cytokine in RWPE-1 cell transformation conceivably through epithelial-mesenchymal transition (EMT), reinforcing VIP role in prostate tumorigenesis.
Fernández-Martínez
Ana B
AB
Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
Bajo
Ana M
AM
Isabel Arenas
M
M
Sánchez-Chapado
Manuel
M
Prieto
Juan C
JC
Carmena
María J
MJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000032:analysis; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000633:toxicity*
D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D019938:Cyclin D1; D014660:Vasoactive Intestinal Peptide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9