期刊
MOLECULAR THERAPY
卷 13, 期 5, 页码 947-955出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2005.11.020
关键词
invasion and metastasis; breast cancer; SCC-S2; VEGFR-2; MMPs; cationic liposomes; SCC-S2 antisense oligo and siRNA; endothelial cell survival
SCC-S2/GG2-1/NDED (approved gene symbol TNFAIP8) is a transcription factor NF-kappa B-inducible, antiapoptotic, and oncogenic molecule. In this study, we examined the role of SCC-S2 in invasion and experimental metastasis. We demonstrate that expression of SCC-S2 cDNA in MDA-MB 435 human breast cancer cells is associated with enhanced invasion in vitro and increased frequency of pulmonary colonization of tumor cells in athymic mice. Systemic treatment of athymic mice with a cationic liposomal formulation of SCC-S2 antisense oligo led to decreased incidence of pulmonary metastasis and inhibition of SCC-S2 expression in vivo. Antisense inhibition of endogenous SCC-S2 expression correlated with decreased expression of VEGF receptor-2 in tumor cells and human lung microvascular endothelial cells and loss of endothelial cell viability. In addition, downregulation of SCC-S2 expression in tumor cells was associated with decreased expression of known metastasis-related molecules MMP-1 and MMP-9. These results demonstrate a novel role for SCC-S2 in tumor progression, involving multiple effectors, and provide a basis for SCC-S2-targeted cancer gene therapy.
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