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Open Access Highly Accessed Research article

In vitro three-dimensional modeling of fallopian tube secretory epithelial cells

Kate Lawrenson1, Maria Notaridou2, Nathan Lee1, Elizabeth Benjamin3, Ian J Jacobs4, Christopher Jones2 and Simon A Gayther1*

  • * Corresponding author: Simon A Gayther gayther@usc.edu

  • † Equal contributors

Author Affiliations

1 Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, California

2 Gynaecological Cancer Research Laboratories, UCL EGA Institute for Women’s Health, University College London, The Paul O’Gorman Building, Gower Street, London WC1E 6DD, UK

3 Department of Histopathology, Cancer Institute, University College London, Rockefeller Building, University Street, London WC1E 6JJ, UK

4 Faculty of Medical and Human Sciences, 1st Floor, Innovation Centre, Core Technology Facility, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK

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BMC Cell Biology 2013, 14:43  doi:10.1186/1471-2121-14-43

Published: 27 September 2013

Abstract

Background

Fallopian tube secretory epithelial cells (FTSECs) have been implicated as a cell-of-origin for high-grade serous epithelial ovarian cancer. However, there are relatively few in vitro models of this tissue type available for use in studies of FTSEC biology and malignant transformation. In vitro three-dimensional (3D) cell culture models aim to recreate the architecture and geometry of tissues in vivo and restore the complex network of cell-cell/cell-matrix interactions that occur throughout the surface of the cell membrane.

Results

We have established and characterized 3D spheroid culture models of primary FTSECs. FTSEC spheroids contain central cores of hyaline matrix surrounded by mono- or multi-layer epithelial sheets. We found that 3D culturing alters the molecular characteristics of FTSECs compared to 2D cultures of the same cells. Gene expression profiling identified more than a thousand differentially expressed genes between 3D and 2D cultures of the same FTSEC lines. Pathways significantly under-represented in 3D FTSEC cultures were associated with cell cycle progression and DNA replication. This was also reflected in the reduced proliferative indices observed in 3D spheroids stained for the proliferation marker MIB1. Comparisons with gene expression profiles of fresh fallopian tube tissues revealed that 2D FTSEC cultures clustered with follicular phase tubal epithelium, whereas 3D FTSEC cultures clustered with luteal phase samples.

Conclusions

This 3D model of fallopian tube secretory epithelial cells will advance our ability to study the underlying biology and etiology of fallopian tube tissues and the pathogenesis of high-grade serous epithelial ovarian cancer.

Keywords:
Fallopian tube secretory epithelial cells; Gene expression microarray; Three-dimensional in vitro models; Tissue microenvironment; Ovarian cancer