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438. Endoglin (CD105) silencing mediated by shRNA under the control of Endothelin-1 promoter for targeted gene therapy of MelanomaNataša Tešić, Urška Kamenšek, Gregor Serša, Simona Kranjc Brezar, Monika Savarin, Urša Lampreht Tratar, Véronique Préat, Gaëlle Vandermeulen, Miha Butinar, Boris Turk, Maja Čemažar, 2015, original scientific article Abstract: Endoglin (CD105), a transforming growth factor (TGF)-% coreceptor, and endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor endothelial and melanoma cells. Their targeting is therefore a promising therapeutic approach for melanoma tumors. The aim of our study was to construct a eukaryotic expression plasmid encoding the shRNA molecules against CD105 under the control of endothelin-1 promoter and to evaluate its therapeutic potential both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA against CD105 under the control of the constitutive U6 promoter was used as a control. We demonstrated the antiproliferative and antiangiogenic effects of both plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence that targeting melanoma with shRNA molecules against CD105 under the control of endothelin-1 promoter is a feasible and effective treatment, especially for the reduction of metastatic spread.
Keywords: melanoma, electroporation, endoglin (CD105), endothelin-1, gene therapy
Published in RUP: 14.10.2015; Views: 3795; Downloads: 131
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