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

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 Munster 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. (Fertil Steril (R) 2016; 106: 378-85. (C) 2016 by American Society for Reproductive Medicine.)