Syndecan-1 knockdown in endometrial epithelial cells alters their apoptotic protein profile and enhances the inducibility of apoptosis.
Endometrial epithelial cells are known to undergo apoptosis during trophoblast invasion. We postulate that the cell surface molecule Syndecan-1 which is expressed on endometrial cells and syncytiotrophoblast is important for implantation in general and especially for induction of maternal cell apoptosis during trophoblast invasion because Syndecan-1's influence on apoptotic susceptibility of cancer cells is already described in the literature. Using the human endometrial epithelial cell line RL95-2, a new stable cell line with Syndecan-1 knockdown was generated. Via antibody array analysis, a significant decrease in the expression of anti-apoptotic proteins like inhibitors of apoptosis, Clusterin, heme oxygenase (HO-2), heat shock protein (HSP)27 and -70 and Survivin due to the Syndecan-1 knockdown was discovered. Correspondingly, active Caspase-3 as an indicator for apoptosis was increased more severely in these cells compared with unmodified RL95-2 after treatment with implantation-related stimuli, which are the cytokines interleukin-1β, interferon-γ, tumor necrosis factor-α and transforming growth factor-β1 and an anti-Fas antibody. Furthermore, a treatment with a combination of all factors caused a higher Caspase-3 induction compared with each single treatment. These results demonstrate that Syndecan-1 is involved in the control of apoptosis in RL95-2 cells and therefore may affect the fine tuning of apoptosis in endometrial epithelium regulating the embryo's invasion depth as a crucial step for regular implantation followed by successful pregnancy.
Department of OB/GYN and REI (UniKiD), Medical Center University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany boeddeker@unikid.de.
S J
SJ
Boeddeker
Department of OB/GYN and REI (UniKiD), Medical Center University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
D M
DM
Baston-Buest
Department of OB/GYN and REI (UniKiD), Medical Center University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
O
O
Altergot-Ahmad
Department of OB/GYN and REI (UniKiD), Medical Center University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
J S
JS
Kruessel
Department of OB/GYN and REI (UniKiD), Medical Center University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
A P
AP
Hess
D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D040081:Protein Array Analysis; D015398:Signal Transduction; D053668:Syndecan-1 / Q000172:deficiency* / Q000235:genetics
C495242:CLU protein, human; D051152:Clusterin; D016207:Cytokines; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D053148:Caspase 3
Fas; IAPs; RL95-2; embryo; implantation