Construction of antisense MT1-MMP vector and its inhibitory effects on invasion of human ovarian cancer cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) plays crucial roles in tumor cell growth, invasion, and angiogenesis. To clarify whether the endogenously expressed MT1-MMP in metastatic human ovarian carcinoma cell lines SKOV3 plays a critical role in tumor cell invasiveness, antisense MT1-MMP cloned in eukaryotic expression vector pMMP14as was transferred into SKOV3 cells. 48h after transfection, decreased expression of endogenous MT1-MMP protein was detected in pMMP14as-transfected SKOV3 cells and the activation of pro-MMP2 was inhibited markedly. The mean percentage of invasive cells was (62.50 +/- 5.30) % in pMMP14as-transfected cells, which was obviously less than that (97.20 +/- 6.90) % in the control. Thus, antisense MT1-MMP effectively inhibited the endogenous MT1-MMP expression and the invasiveness in SKOV3 cells, suggesting that MT1-MMP may be a therapeutic target molecule for human invasive ovarian cancers.