1. In vitro three-dimensional modeling of fallopian tube secretory epithelial cells.
- Author
-
Lawrenson K, Notaridou M, Lee N, Benjamin E, Jacobs IJ, Jones C, and Gayther SA
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Adult, Aged, Animals, Cell Proliferation, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, DNA Replication, Endometrial Neoplasms genetics, Endometrial Neoplasms metabolism, Endometrial Neoplasms pathology, Epithelial Cells pathology, Fallopian Tubes pathology, Female, Follicular Phase genetics, Follicular Phase metabolism, Gene Expression Profiling, Humans, Luteal Phase genetics, Luteal Phase metabolism, Middle Aged, Neoplasm Proteins metabolism, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Primary Cell Culture, Signal Transduction, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Cell Culture Techniques methods, Cell Transformation, Neoplastic metabolism, Epithelial Cells metabolism, Fallopian Tubes metabolism, Gene Expression Regulation, Neoplastic, Neoplasm Proteins genetics
- 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.
- Published
- 2013
- Full Text
- View/download PDF