Over-expression of stomatin causes syncytium formation in nonfusogenic JEG-3 choriocarcinoma placental cells.
Placental trophoblast differentiation involves the continuous fusion of mononuclear cytotrophoblasts. However, except for syncytin, little is known about the detailed mechanisms underlying trophoblast fusion. A previous study indicated that lipid rafts play an important role in HTLV-1 syncytium formation. To identify proteins that may be involved in placental trophoblast differentiation, we examined stomatin, an important lipid-raft protein that localizes to detergent-resistant membrane domains. The syncytium and human chorionic gonadotropin (β-hCG; a marker of placental trophoblast differentiation) were visualized by immunofluorescence staining. We found that overexpression of stomatin in the nonfusogenic JEG-3 cell line caused syncytium formation and increased the fusion index of cells. Treating these cells with N(6) ,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate further increased cell fusion by stomatin. β-hCG was found in a few JEG-3 cells overexpressing stomatin at 48 h, and its levels increased dramatically at 72 h along with the formation of the multinuclear syncytium. RNA interference was used to decrease stomatin expression in BeWo cells, a fusogenic human choriocarcinoma cell line. After knockdown for 72 h, stomatin levels decreased by almost 95%. The fusion indexes of control and stomatin-knockdown cells at 72 h were 9.4 and 6.5%, respectively. Our data indicated that stomatin could trigger syncytium formation and upregulate β-hCG for cell fusion in nonfusogenic JEG-3 cells. Downregulation of stomatin slightly inhibited the fusion index of fusogenic BeWo cells. Thus, these data suggested that stomatin plays an important role in trophoblast differentiation.
Institute of Biophotonics, National Yang-Ming University, No. 155, Sec. 2, Linong, Street, Taipei, Taiwan, 112,, ROC.
Tung-Wei
TW
Chen
Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.
Hong-Wen
HW
Liu
Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.
Yi-Jia
YJ
Liou
Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.|Institute of Biochemistry, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.|Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.
Jui-Hao
JH
Lee
Institute of Biophotonics, National Yang-Ming University, No. 155, Sec. 2, Linong, Street, Taipei, Taiwan, 112,, ROC.|Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan, 112,, ROC.|Department of Health, New Taipei City Government, Taipei, Taiwan.
Chi-Hung
CH
Lin
D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D006063:Chorionic Gonadotropin; D005260:Female; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D034622:RNA Interference; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D006063:Chorionic Gonadotropin; D015686:Gene Products, env; D008565:Membrane Proteins; D011257:Pregnancy Proteins; C036860:STOM protein, human; C405335:syncytin; D003994:Bucladesine
cytotrophoblast; human chorionic gonadotropin; lipid raft; stomatin; syncytium