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Inhibition of Hyaluronic Acid Synthesis Decreases Endometrial Cell Attachment, Migration, and Invasion

Overview
Journal Reprod Sci
Publisher Springer
Date 2020 Feb 5
PMID 32016803
Citations 4
Authors
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Abstract

To characterize the effects of 4-methylumbelliferone (4-MU) on expression of the hyaluronic acid (HA) system and on attachment, migration, and invasion of endometrial epithelial (EECs) and stroma cells (ESCs) to peritoneal mesothelial cells (PMCs), this in vitro study was performed in an Academic Center. De-identified endometrial tissue samples used were from reproductive-aged women. EECs and ESCs isolated from menstrual endometrial biopsies were treated with 4-MU or vehicle. Real-time polymerase chain reaction and western blot were used to assess expression of HA synthases (HAS), hyaluronidase, and standard CD44. Established in vitro assays were used to assess attachment, migration, and invasion with and without treatment with 4-MU. Chi square and Student's t-test were used to analyze the results as appropriate. The addition of 4-MU decreased mRNA and protein expression of HAS 2, HAS 3, and CD44 in EECs and ESCs compared to control. Treatment with 4-MU also decreased attachment, migration, and invasion of EECs and ESCs to PMCs compared to control. 4-MU decreases endometrial cell adhesion, migration, and invasion to PMCs. This effect appears to be mediated by a decrease in HAS 2, HAS 3, and CD44. 4-MU is a potential treatment for endometriosis. Future in vivo studies are needed to evaluate 4-MU as a therapeutic agent for endometriosis.

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References
1.
Nair H, Luthra R, Kirma N, Liu Y, Flowers L, Evans D . Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Cancer Res. 2005; 65(23):11164-73. DOI: 10.1158/0008-5472.CAN-05-1087. View

2.
Lucidi R, Witz C, Chrisco M, Binkley P, Shain S, Schenken R . A novel in vitro model of the early endometriotic lesion demonstrates that attachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. Fertil Steril. 2005; 84(1):16-21. DOI: 10.1016/j.fertnstert.2004.10.058. View

3.
Kakizaki I, Kojima K, Takagaki K, Endo M, Kannagi R, Ito M . A novel mechanism for the inhibition of hyaluronan biosynthesis by 4-methylumbelliferone. J Biol Chem. 2004; 279(32):33281-9. DOI: 10.1074/jbc.M405918200. View

4.
Nagase H, Kudo D, Suto A, Yoshida E, Suto S, Negishi M . 4-Methylumbelliferone Suppresses Hyaluronan Synthesis and Tumor Progression in SCID Mice Intra-abdominally Inoculated With Pancreatic Cancer Cells. Pancreas. 2016; 46(2):190-197. PMC: 5266424. DOI: 10.1097/MPA.0000000000000741. View

5.
Griffith J, Liu Y, Tekmal R, Binkley P, Holden A, Schenken R . Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants. Fertil Steril. 2009; 93(6):1745-9. PMC: 2864724. DOI: 10.1016/j.fertnstert.2008.12.012. View