In vitro three-dimensional modeling of fallopian tube secretory epithelial cells.
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.
Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, California. gayther@usc.edu.
Kate
K
Lawrenson
Maria
M
Notaridou
Nathan
N
Lee
Elizabeth
E
Benjamin
Ian J
IJ
Jacobs
Christopher
C
Jones
Simon A
SA
Gayther
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004261:DNA Replication; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005187:Fallopian Tubes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005498:Follicular Phase / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008183:Luteal Phase / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases