The hyaluronan synthesis inhibitor 4-methylumbelliferone inhibits cell proliferation and wound healing on in vitro endometriosis models

OLIVARES C; CHIAPPINI F; MC CORMACK B; MADANES D; IBAÑEZ PADILLA MC; RANDI A; BARAÑAO RI; MERESMAN G

Congreso; International Federation of Placenta Associations 2019 (IFPA2019), 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta (VIII SLIMP); 2019

Study question: What is the effect of 4-methylumbelliferone (4MU) on cell proliferation, wound healing process and gelatinase activity on human endometrial stromal (t-HESC) or epithelial (ECC-1) cell lines?Summary answer: Cell proliferation and wound healing were significantly inhibited by 4MU, whereas MMP-2 and MMP-9 activity would not be modulated by this treatment.What is known already: Endometriosis is a benign gynecological disease affecting 10% of women of reproductive age, characterized by the presence of endometriotic foci outside the uterine cavity. We have already demonstrated that 4MU has antiangiogenic properties in two angiogenesis models of endometriosis, both in vitro and in vivo, and it has been reported that binding of hyaluronan to its CD44 receptor is involved in proliferation, migration and invasion in cancer cells.Study design, size and duration: We evaluated the effect of 0.1, 0.5, 1, 2 and 4mM 4MU on in vitro endometriosis models comparing control versus treatment. Cell proliferation was assessed on ECC-1 (n=10) and t-HESC (n=5), and gelatinase activity (n=2) and wound healing (n=6) process were evaluated on t-HESC. For cell proliferation and gelatinase activity cells were treated for 24hs and for the wound healing assay cells were treated during 20hs.Participants/materials, setting, methods: t-HESC and ECC-1 endometrial cell lines were stimulated with different concentrations of 4MU. Cell proliferation was evaluated after 24hs with the cell proliferation reagent WST-1. The area of a scratch closed by the t-HESC was calculated in a wound healing assay, for this purpose photomicrographs were taken at time 0h and time 20hs; and the gelatinase activity in conditioned media of t-HESC was evaluated by zimography. Only p