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      Role of the Exosome in Ovarian Cancer Progression and Its Potential as a Therapeutic Target

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          Abstract

          Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30–150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and lipids. Furthermore, therapeutic applications of exosomes as drug cargo delivery are attracting research interest because exosomes are stabilized in circulation. This review highlights the functions of exosomes in each process of the peritoneal dissemination of ovarian cancer and discusses their potential for cancer therapeutics.

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          Biogenesis and secretion of exosomes.

          Joanna Kowal, Mercedes Tkach, Clotilde Théry (2014)
          Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression.

            Mina Bissell, William C. Hines (2011)
            Tumors are like new organs and are made of multiple cell types and components. The tumor competes with the normal microenvironment to overcome antitumorigenic pressures. Before that battle is won, the tumor may exist within the organ unnoticed by the host, referred to as 'occult cancer'. We review how normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state. We also include a discussion of how this information is being tailored for clinical use.
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              Is Open Access

              Epidemiology of ovarian cancer: a review

              Brett M. Reid, Jennifer B. Permuth, Thomas Sellers (2017)
              Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology, primary prevention, early detection, and possibly even therapeutic strategies.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 10 August 2019
                Publication date Collection: August 2019
                Volume: 11
                Issue: 8
                Electronic Location Identifier: 1147
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan
                [2 ]Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
                [3 ]Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Biomedical Research Building II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA
                Author notes
                [* ]Correspondence: daasawada@ 123456gyne.med.osaka-u.ac.jp ; Tel.: +81-6-6879-3351
                Author information
                https://orcid.org/0000-0002-5473-2069
                https://orcid.org/0000-0001-7384-2581
                Article
                Publisher ID: cancers-11-01147
                DOI: 10.3390/cancers11081147
                PMC ID: 6721530
                PubMed ID: 31405096
                SO-VID: d2e0e2d6-20d3-4be2-8a51-8cc620c8176f
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 30 June 2019
                Date accepted : 07 August 2019
                Categories
                Subject: Review

                Keywords: exosome,ovarian cancer,peritoneal dissemination
                Data availability:
                Keywords: exosome, ovarian cancer, peritoneal dissemination

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