Summary
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 cukaryotic 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.
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References
Sounni N E, Devy L, Hajitou Aet al. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J, 2002, 16(6):555
Rozanov D V, Savinov A Y, Golubkov V Set al. Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system. J Biol Chem, 2004, 279(45):46551
Heussen C, Dowdle E B. Electrophoretic analysis of plasminogen activation in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem, 1980, 102(1):196
Graves L E, Ariztia E V, Navari J Ret al. Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res, 2004, 64(19):7045
Ueda J, Kajita M, Suenaga Net al. Sequence-specific silencing of MT1-MMP expression suppresses tumor cell migration and invasion: importance of MT1-MMP as a therapeutic target for invasive tumors. Oncogene, 2003, 22(54):8716
Seiki M. Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett, 2003, 194 (1):1
Hotary K B, Allen E D, Brooks P Cet al. Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell, 2003, 14(1):33
Hotary K, Allen E, Weiss S Jet al. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol, 2000, 149(6):1309
Stein C A, Cheng Y V. Antisense oligonucleotides as therapeutic agents is the bullet really magical. Science, 1993, 261(5124):1004
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WU Mingfu, male, born in 1972, M.D., Ph.D.
This study was sapported by grants from National Basic Research program “973” (No.2002CB513107).
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Mingfu, W., Yanyan, S., Lin, X. et al. Construction of antisense MT1-MMP vector and its inhibitory effects on invasion of human ovarian cancer cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 25, 715–717 (2005). https://doi.org/10.1007/BF02896180
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DOI: https://doi.org/10.1007/BF02896180