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Molecular Human Reproduction, Vol. 8, No. 7, 659-666, July 2002
© 2002 European Society of Human Reproduction and Embryology

Implantation and pregnancy

Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3

Jian Zhang1, Yu-Jing Cao1, Yun-Ge Zhao2, Qing-Xiang Amy Sang2 and En-Kui Duan1,3

1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, P.R. China and 2 Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA

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.

choriocarcinoma JEG-3/matrix metalloproteinases/MMP-26/normal cytotrophoblasts/TIMP-4

3 To whom correspondence should be addressed. E-mail: duane{at}panda.ioz.ac.cn


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