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 invaslve ovarian cancers.

The role of MT1-MMP in the progression and metastasis of osteosarcoma

The dysregulation of Membrane-type 1 matrix metalloproteinase(MT1-MMP)has been extensively studied in numerous cancer types,and plays key roles in angiogenesis,cancer progression,and metastasis.MT1-MMP is a predictor of poor prognosis in osteosarcoma(OS),yet the molecular mechanisms of disease progression are unclear.This review provides a summary of the literature relating to the gene and protein expression of MT1-MMP(MMP-14)in OS clinical samples,evaluates the expression in cell lines and experimental models,and analyses its potential role in the progression and metastasis of OS.In addition,the therapeutic potential of MT1-MMP as a drug target has been assessed.Due to the biological complexity of MMPs,inhibition has proven to be challenging.However,exploiting the expression and proteolytic capacity of MT1-MMP could open new avenues in the search for novel,safer and selective drugs for use in OS.