Ezrin Is Associated with Disease Progression in Ovarian Carcinoma.
OBJECTIVE
Ezrin and p130Cas are structural proteins with an important role in signaling pathways and have been shown to promote cancer dissemination. We previously reported on overexpression of both ezrin and p130Cas in breast carcinoma effusions compared to primary carcinomas. Since ovarian and breast carcinomas share the ability to disseminate by forming malignant effusions, we sought to study the role of these molecules in ovarian carcinoma (OC).


METHODS
OC cell lines were cultured in two different 3-dimensional conditions, on alginate scaffolds and as spheroids, which served as models for solid tumor and malignant effusions, respectively. shRNA was used to reduce protein expression in the cells. The malignant potential was evaluated by chemo-invasion assay, branching capacity on Matrigel and rate of proliferation. Subsequently, clinical specimens of high-grade serous carcinoma effusions, ovarian tumors and solid metastases were analyzed for ezrin and p130Cas expression.


RESULTS
Higher ezrin expression was found in cells composing the spheroids compared to their counterparts cultured on alginate scaffold and in clinical samples of malignant effusions compared to solid tumors. In addition, reduced Ezrin expression impaired the invasion ability and the branching capacity of OC cells to a greater extent than reduced p130Cas expression. However, ezrin and p130Cas expression in effusions was unrelated to clinical outcome.


CONCLUSIONS
The 3-dimensional cell cultures were found to mimic the different tumor sites and be applicable as a model. The in vitro results concur with the clinical specimen analysis, suggesting that in OC, the role of ezrin in disease progression is more pronounced than that of p130Cas.
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.|Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.
Vered
V
Horwitz
Departments of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, Oslo, Norway.|Gynecologic Oncology Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Ben
B
Davidson
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Dganit
D
Stern
University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, Oslo, Norway.
Claes G
CG
Tropé
Department of Pharmaceutical Engineering, Azrieli College of Engineering, Jerusalem, Israel.
Tali
T
Tavor Re'em
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.|David R. Bloom Center for Pharmacy at The Hebrew University of Jerusalem, Jerusalem, Israel.|Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Jerusalem, Israel.
Reuven
R
Reich
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D050719:Crk-Associated Substrate Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular; D000099149:Ezrin
D014408:Biomarkers, Tumor; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D034741:RNA, Small Interfering; D000099149:Ezrin