Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3.
The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is critical for embryo implantation. Disturbance of this balance may lead to tumour metastasis. To understand the roles of MMP-26 and TIMP-4 in physiological and pathological invasion, the expression of these proteins in normal human cytotrophoblast cells and in a malignant choriocarcinoma cell line, JEG-3, was investigated. MMP-26 and TIMP-4 proteins were detected in the cytoplasm of these cells. The expression levels of MMP-26 mRNA and protein in JEG-3 cells were significantly higher than those in the cytotrophoblasts; conversely, the expression levels of TIMP-4 mRNA and protein were much lower in JEG-3 cells than those in cytotrophoblasts (P < 0.01). Enzyme inhibition studies demonstrated that TIMP-4 was a potent inhibitor of MMP-26 with an IC50 value of 0.4 nmol/l. This study confirms that MMP-26 is an epithelial enzyme and suggests that MMP-26 and TIMP-4 may play a role in tissue-remodelling processes associated with placentation and tumour progression, and that a higher MMP-26 to TIMP-4 ratio may promote cancer invasion.
Zhang
Jian
J
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, P.R. China.
Cao
Yu-Jing
YJ
Zhao
Yun-Ge
YG
Sang
Qing-Xiang Amy
QX
Duan
En-Kui
EK
D002460:Cell Line; D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D053505:Matrix Metalloproteinases, Secreted; D010920:Placenta / Q000378:metabolism; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D014327:Trophoblasts / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C410599:MMP26 protein, human