title: Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma.
abstract: The melanoma cell adhesion molecule (MCAM) is involved in melanoma development and its progression, including invasiveness, metastatic potential and angiogenesis. Therefore, MCAM represents a potential target for gene therapy of melanoma, whose expression could be hindered with posttranscriptional specific gene silencing with RNA interference technology. In this study, we constructed a plasmid DNA encoding short hairpin RNA against MCAM (pMCAM) to explore the antitumor and antiangiogenic effects. The experiments were performed in vitro on murine melanoma and endothelial cells, as well as in vivo on melanoma tumors in mice. The antiproliferative, antimigratory, antiangiogenic and antitumor effects were examined after gene therapy with pMCAM. Gene delivery was performed by magnetofection, and its efficacy compared to gene electrotransfer. Gene therapy with pMCAM has proved to be an effective approach in reducing the proliferation and migration of melanoma cells, as well as having antiangiogenic effect in endothelial cells and antitumor effect on melanoma tumors. Magnetofection as a developing nonviral gene delivery system was effective in the transfection of melanoma cells and tumors with pMCAM, but less efficient than gene electrotransfer in in vivo tumor gene therapy due to the lack of antiangiogenic effect after silencing Mcam by magnetofection.
authors.affiliation: Kolektor Group, Nanotesla Institute Ljubljana, Ljubljana, Slovenia.
authors.forename: Lara
authors.initials: L
authors.lastname: Prosen
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Markelc
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Dolinsek
authors.affiliation: Kolektor Group, Nanotesla Institute Ljubljana, Ljubljana, Slovenia.
authors.forename: Branka
authors.initials: B
authors.lastname: Music
authors.affiliation: 1] Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia [2] Department of Natural and Medical Subjects, University of Primorska, Faculty of Health Sciences, Izola, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa