Syndecan-4 expression is upregulated in endometriosis and contributes to an invasive phenotype

Syndecan-4 is upregulated in eutopic endometrium of patients with endometriosis and may promote invasive cell behavior via Rac1, MMP3, and ATF-2.

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Volume 106, Issue 2, Pages 378-385

Authors:

Anca Chelariu-Raicu, M.D., Cornelia Wilke, Ph.D., Melanie Brand, M.Sc., Anna Starzinski-Powitz, Ph.D., Ludwig Kiesel, M.D., Ph.D., Andreas N. Schüring, M.D., Martin Götte, Ph.D.

Abstract:

Objective

To study the expression and function of syndecan-4 in endometriosis.

Design

Histopathological investigation of eutopic endometrium and experimental laboratory study on a cell line derived from epithelial endometriotic cells (12Z).

Setting

University hospital laboratory.

Patient(s)

One hundred six women (62 controls/44 endometriosis) from the IVF center of Münster University Hospital aged 23–44 undergoing Pipelle biopsy and diagnostic exploratory laparoscopy.

Intervention(s)

Eutopic endometrial tissue was investigated by immunohistochemistry for the expression of syndecan-4. The human endometriotic cell line 12Z was transiently transfected with syndecan-4 small interfering RNA and investigated for changes in cell behavior.

Main Outcome Measure(s)

Syndecan-4 expression in eutopic endometrium was evaluated immunohistochemically in endometrial glands and stroma. Scoring results were correlated with the stages of the menstrual cycle and presence or absence of endometriosis. Quantitative polymerase chain reaction was used to measure syndecan-4-dependent expression changes of MMP2, MMP3, MMP9, Rac1, and ATF2. Altered cell behavior was monitored by matrigel invasion assays and cell viability assays.

Result(s)

Syndecan-4 expression was significantly higher in the glands and stroma of patients with endometriosis compared with controls, whereas no menstrual cycle–dependent expression was observed. In 12Z cells, syndecan-4 depletion did not affect cell viability but resulted in a significantly reduced matrigel invasiveness and reduced expression of the small GTPase Rac1, the transcription factor ATF-2, and MMP3.

Conclusion(s)

The upregulation of syndecan-4 in the eutopic endometrium of endometriosis patients may facilitate the pathogenetic process by promoting invasive cell growth via Rac1, MMP3, and ATF-2.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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