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      Epithelial–Mesenchymal Transition in Ovarian Carcinoma

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          Abstract

          Ovarian cancer is the most lethal gynecologic malignancy, with the majority of patients dying within 5 years of diagnosis. This poor survival of patients diagnosed with this malignancy is attributed to diagnosis at advanced stage, when the tumor has metastasized, and to chemotherapy resistance, either primary or developing along tumor progression. However, ovarian carcinomas, constituting the vast majority of ovarian cancers, additionally have unique biology, one aspect of which is the ability to co-express epithelial and mesenchymal determinants. epithelial–mesenchymal transition (EMT), a physiological process by which mesenchymal cells are formed and migrate to target organs during embryogenesis, is involved in cancer cell invasion and metastasis. However, these changes do not fully occur in ovarian carcinoma, and are even reversed in tumor cells present in malignant peritoneal and pleural effusions. This review summarizes current knowledge in this area, including the characteristics of EMT related to adhesion, transcriptional regulation and chemoresistance, and their clinical relevance, as well as the recently observed regulation of EMT by microRNA.

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          Most cited references113

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.

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              Inflammation and EMT: an alliance towards organ fibrosis and cancer progression

              Recent advances in our understanding of the molecular pathways that govern the association of inflammation with organ fibrosis and cancer point to the epithelial to mesenchymal transition (EMT) as the common link in the progression of these devastating diseases. The EMT is a crucial process in the development of different tissues in the embryo and its reactivation in the adult may be regarded as a physiological attempt to control inflammatory responses and to ‘heal’ damaged tissue. However, in pathological contexts such as in tumours or during the development of organ fibrosis, this healing response adopts a sinister nature, steering these diseases towards metastasis and organ failure. Importantly, the chronic inflammatory microenvironment common to fibrotic and cancer cells emerges as a decisive factor in the induction of the pathological EMT.

                Author and article information

                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Research Foundation
                2234-943X
                10 April 2012
                2012
                : 2
                : 33
                Affiliations
                [1] 1simpleDivision of Pathology, Norwegian Radium Hospital, Oslo University Hospital Oslo, Norway
                [2] 2simpleFaculty of Medicine, University of Oslo Oslo, Norway
                [3] 3simpleSection of Gynecologic Oncology, Division of Gynecology and Obstetrics, Norwegian Radium Hospital, Oslo University Hospital Oslo, Norway
                [4] 4simpleInstitute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem Jerusalem, Israel
                [5] 5simpleDavid R. Bloom Center for Pharmacy and the Brettler Center for Pharmacology, The Hebrew University of Jerusalem Jerusalem, Israel
                Author notes

                Edited by: Nicolas Wentzensen, National Cancer Institute, USA

                Reviewed by: Britton Trabert, National Institutes of Health, USA; Ie-Ming Shih, Johns Hopkins Medical Institutions, USA

                *Correspondence: Ben Davidson, Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway. e-mail: bend@ 123456medisin.uio.no

                This article was submitted to Frontiers in Women’s Cancer, a specialty of Frontiers in Oncology.

                Article
                10.3389/fonc.2012.00033
                3356037
                22655269
                7ca899b1-d083-413c-80dd-8c94a5e47934
                Copyright © 2012 Davidson, Tropé and Reich.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                History
                : 07 January 2012
                : 21 March 2012
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 138, Pages: 13, Words: 12524
                Categories
                Oncology
                Review Article

                Oncology & Radiotherapy
                chemotherapy,epithelial–mesenchymal transition,prognosis,ovarian carcinoma,metastasis,mesenchymal–epithelial transition,tumor progression

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