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.
Wu
Mingfu
M
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Shi
Yanyan
Y
Xi
Lin
L
Li
Qiong
Q
Liao
Guo-Nin
GN
Han
Zhi-Qiang
ZQ
Lu
Yun-Ping
YP
Ma
Ding
D
D045744:Cell Line, Tumor; D005057:Eukaryotic Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis* / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D016376:Oligonucleotides, Antisense; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; D053504:Matrix Metalloproteinases, Membrane-Associated; D053511:Matrix Metalloproteinase 14