Article Text

Download PDFPDF

58 SYNDECAN-1 Inhibition reverses the pre-malignant phenotype of endometrioma through TGF-BETA signalling: potential implications in endometriosis associated ovarian cancer
  1. S Ponandai-Srinivasan1,
  2. M Saare2,
  3. NR Boggavarapu1,
  4. S Ehström3,
  5. PA Garcìa-Uribe1,
  6. A Salumets2,4,
  7. M Götte5,
  8. PG Lalitkumar1 and
  9. K Gemzell-Danielsson1
  1. 1Karolinska Institute, Department of Women’s and Children’s health, Stockholm, Sweden
  2. 2University of Tartu, Department of Obstetrics and Gynecology, Tartu, Estonia
  3. 3Sofiahemmet Hospital, Ultragyn, Stockholm, Sweden
  4. 4University of Helsinki and Helsinki University Hospital, Department of Obstetrics and Gynaecology, Helsinki, Finland
  5. 5Muenster University- Medical Center, Department of Gynecology and Obstetrics, Meunster, Germany


Objectives Transforming growth factor-beta (TGF-β) is abundantly expressed in peritoneal fluid and endometrioma of women with endometriosis. Similarly, transmembrane proteoglycans of the Syndecan family (SDC), act as co-receptors for growth signalling factors and are aberrantly expressed in endometriotic tissues. Here, we aim to investigate the regulation of SDC-1 upon induced activation with TGF-β in vitro, to better understand their interactions and involvement in the pathophysiology of endometriosis.

Methods Endometrioma biopsies (n=15) were obtained from women diagnosed with endometriosis and not received any hormonal treatment. Tissue biospies were investigated for intra-patient heterogeneity using pre-validated panel of stem- and cancer- cell signalling genes. Simultaneously, patient-derived endometriotic stem/stromal cells (CD90+ CD73+CD105+, SC+) were allowed to generate 3D-spheroids in absence or presence of rhTGF-β or TGFBRI/II inhibitor Ly2109761 in vitro; assessed for its influence on SDC-1 expression, proliferation and invasive behaviour. Further, transcriptomic signatures after 3D-spheroid invasion was evaluated upon combining SDC-1 gene silencing with rhTGF-β treatment.

Results Clustering analysis from endometriotic tissue gene expression revealed in 2/15 samples (referred to as Endo-hi) aberrant expression of molecules of TGF-β signalling (TGF-β1, ESR1, CTNNB1, SNAI1, BMI1) which grouped separately from low expression samples (Endo-lo) by >95% CI. 3D-spheroids from Endo-hi SC+ exposed to rhTGF-β treatment showed increased SDC-1 expression and higher 3D-spheroid invasion compared to Endo-lo SC+. However, rhTGFβ treatment following SDC-1 gene silencing reversed the higher 3D-invasion potential and exhibited downregulation of cancer associated pathways.

Conclusions Modulation of SDC-1 reverses the pre-malignant phenotype of endometrioma and may reduce the potential risk for endometriosis associated ovarian cancer.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.