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.