title: Novel three-dimensional in vitro models of ovarian endometriosis.
abstract: BACKGROUND
  Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures.
  
  
  METHODS
  A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR.
  
  
  RESULTS
  In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions.
  
  
  CONCLUSIONS
  To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.
authors: Doerthe
authors: D
authors: Brueggmann
authors: Claire
authors: C
authors: Templeman
authors: Anna
authors: A
authors: Starzinski-Powitz
authors: Nagesh P
authors: NP
authors: Rao
authors: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, Harlyne Norris Research Tower, NRT2517G, 1450 Biggy Street, Los Angeles, California 90033, USA. gayther@usc.edu.
authors: Simon A
authors: SA
authors: Gayther
authors: Kate
authors: K
authors: Lawrenson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012720:Severity of Illness Index; D018874:Spheroids, Cellular; D013997:Time Factors
chemical_list: D015415:Biomarkers