title: Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic potential in human clear cell renal cell carcinoma.
abstract: Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC(1/2)-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Vacas
authors.forename: Ana M
authors.initials: AM
authors.lastname: Bajo
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Chapado
authors.forename: Juan C
authors.initials: JC
authors.lastname: Prieto
authors.forename: María J
authors.initials: MJ
authors.lastname: Carmena
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D052002:NF-kappa B p50 Subunit; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D014660:Vasoactive Intestinal Peptide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9