Hum. Reprod. Advance Access published online on August 24, 2007
Human Reproduction, doi:10.1093/humrep/dem249
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Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro
1 Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan 2 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan 3 Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, No. 1, Sec. 1 Jen-Ai Road, Taipei 100, Taiwan 4 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
5 Correspondence address. Tel: +886-2-23123456; Fax: +886-2-23915292; E-mail: mchuang{at}ntu.edu.tw
BACKGROUND: Trophoblast invasion is crucial for the development of normal placentas. Mucins are suggested to be involved in cancer invasion. However, the function of mucins in trophoblast invasion has never been reported. This study was to investigate the expression of mucin (MUC) 15 in human placenta and its role in trophoblast invasion.
METHODS: MUC15 mRNA in human tissues was analyzed by Northern blot. MUC15 mRNA and protein in human placenta were detected by real-time RT-PCR and Western blot, respectively. The distribution of MUC15 was revealed by immunohistochemistry. The effects of MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and JEG-3 cells.
RESULTS: MUC15 was expressed most highly in human placenta. MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC15 was found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasion of JAR and JEG-3 cells by 87.5 ± 1.1 and 83.8 ± 5.7%, respectively, versus control, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05).
CONCLUSIONS: Differential expression of MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion.
Key words: mucin/trophoblast/invasion/tissue inhibitor of metalloproteinases/placenta
Submitted on December 4, 2006; resubmitted on June 23, 2007; accepted on June 29, 2006.
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