Stimulation of progesterone, estradiol and cortisol in trophoblast tumor bewo cells by glycodelin A N-glycans.

BACKGROUND The immunosuppressive protein glycodelin A (GdA) is secreted by a large number of gynaecological tumors. GdA has a unique glycosylation, including fucosylated LacdiNAc structures. Trophoblast tumor cells produce a variety of steroid hormones and human chorionic gonadotropin (hCG). The purpose of this study was to investigate the effect of GdA N-glycans on hCG, cortisol, estradiol and progesterone release by the chorion carcinoma cell line BeWo in vitro. MATERIALS AND METHODS Chorionic carcinoma cells of the cell line BeWo (1 x 10(6) cells/ml) were cultivated in the presence of 25 mmol/ml glycodelin A and 25 mmol/ml glycodelin A N-glycans RH-3, RH-4 and RH-5 for up to 72 h. Unstimulated BeWo cells were used as controls. After 24 h, 48 h and 72 h, 1 ml cell culture supernatant was removed, stored at -25 degrees C and replaced by fresh medium. All experiments were carried out at least in triplicates. Collected cell culture supernatants were analysed for hCG, progesterone, estradiol (E2) and cortisol concentration. RESULTS The production of estradiol, cortisol and progesterone were increased in GdA N-glycan-treated cell cultures as compared to untreated BeWo cell cultures. GdA N-glycans did not stimulate hCG production in BeWo cells. A significant increase in E2 secretion was observed in BeWo cells incubated with glycodelin A and glycodelin A N-glycans (RH-3: 2.6% E2 increase compared to control, p = 0.401; RH-4: 8.9% increase, p = 0.012; RH-5: 4% increase, p = 0.017; glycodelin: 7.7% increase, p = 0.017). Although an increase in progesterone secretion was observed in BeWo cells incubated with glycodelin A (9.0%) and glycodelin A N-glycans (RH-3: 16.2%, RH-4: 2.8%, RH-5: 8.7%) compared to controls, these differences were not statistically significant. CONCLUSION Estradiol, cortisol and progesterone are hormone markers for BeWo trophoblast tumor cells. The results suggest that GdA with its distinct glycosylation modulates the hormone production of trophoblast tumours.