Three-dimensional in vitro cell biology models of ovarian and endometrial cancer.
OBJECTIVE
This study aims to establish three-dimensional (3D) cell culture models of human ovarian and endometrial cancers and to compare biological and morphological characteristics of these models with those of two-dimensional (2D) models of the same cell lines and the primary tumours.


METHODS
3D models of ovarian and endometrial cancer cell cultures were established using a Rotary Cell Culture System. Immunohistochemical profiling and differential proteomics were used to characterize biological characteristics of multicellular spheroids (MCS) formed from these cultures. These were compared to characteristics of the same cells established in 2D and of the primary tumours from which the cell lines were derived.


RESULTS
MCSs from 3D cell cultures appeared histologically similar to the primary tumours. Immunohistochemical profiling of multiple markers, including CA125, BCL2 and p53, showed that patterns of protein expression in MCSs resemble those of the primary tumours. Proteomic profiling identified several differentially expressed protein markers between 2D and 3D cultures. These included prohibitin, which was down-regulated in 3D cultures suggesting cells proliferate less compared to 2D cultures; and VDAC1 and annexin 4, which were up-regulated in 3D cultures suggesting greater levels of apoptosis in 3D compared to 2D models.


CONCLUSIONS
Establishing 3D models of cancer cell lines is likely to be of value for studying the molecular and biological mechanisms of ovarian/endometrial tumour progression and for testing novel molecular targets for cancer therapy.
Grun
B
B
Gynaecological Cancer Research Laboratory, EGA Institute for Women's Health, University College London, London, UK.
Benjamin
E
E
Sinclair
J
J
Timms
J F
JF
Jacobs
I J
IJ
Gayther
S A
SA
Dafou
D
D
D014408:Biomarkers, Tumor / Q000378:metabolism; D018394:CA-125 Antigen / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002999:Clone Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D016889:Endometrial Neoplasms / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology*; D020543:Proteome / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018874:Spheroids, Cellular / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000951:Antigens, Neoplasm
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D053552:Keratin-7; D019394:Ki-67 Antigen; D020543:Proteome; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; C115012:human epithelial antigen-125; D000951:Antigens, Neoplasm