| Autor: |
Natasa Tesic, Urska Kamensek, Gregor Sersa, Simona Kranjc, Monika Stimac, Ursa Lampreht, Veronique Preat, Gaelle Vandermeulen, Miha Butinar, Boris Turk, Maja Cemazar |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 4, Iss C (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1038/mtna.2015.12 |
| Popis: |
Endoglin (CD105), a transforming growth factor (TGF)-β 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
