Abstract
BackgroundEndometriosis 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.MethodsA 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.ResultsIn 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.ConclusionsTo 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.
Highlights
Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity
We evaluated the expression of several biomarkers and found that EEC16 expressed cytokeratin and vimentin, but did not express N-Cadherin, ERα or P-Cadherin (Figure 1B)
We observed that CDH1 gene expression is significantly lower in human ovarian endometriosis tissues compared to eutopic endometrium, which suggests the lack of E-Cadherin expression by EEC16 is not atypical for ovarian endometriosis (Figure 1C)
Summary
Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity It affects 1 in 10 women of reproductive age. Despite the prevalence of endometriosis and its significant 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. Co-injection of these cells into mice results in peritoneal lesions that recreate histological features of human endometriosis in vivo [8] This particular model has been used to study various aspects of endometriosis cell biology including hormone signaling, cell-cell adhesions, as well as to conduct candidate gene studies [9,10,11]. This model was established from a peritoneal lesion, and there is a real need for additional models that mimic other subtypes of this disease in order to better understand the pathophysiology of endometriosis subtypes, and for the development of new treatment strategies
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