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      An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

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          Abstract

          Metastasis is a complex multistep process that involves critical interactions between cancer cells and a variety of stromal components in the tumor microenvironment, which profoundly influence the different aspects of the metastatic cascade and organ tropism of disseminating cancer cells. Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Evidence has demonstrated that ovarian cancer possesses specific metastatic tropism for the adipose-rich omentum, which has a pivotal role in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity. Considering the distinct biology of ovarian cancer metastasis, the elucidation of the cellular and molecular mechanisms underlying the reciprocal interplay between ovarian cancer cells and surrounding stromal cell types in the adipose-rich metastatic microenvironment will provide further insights into the development of novel therapeutic approaches for patients with advanced ovarian cancer. Herein, we review the biological mechanisms that regulate the highly orchestrated crosstalk between ovarian cancer cells and various cancer-associated stromal cells in the metastatic tumor microenvironment with regard to the omentum by illustrating how different stromal cells concertedly contribute to the development of ovarian cancer metastasis and metastatic tropism for the omentum.

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          Tumor metastasis: molecular insights and evolving paradigms.

          Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Microenvironmental regulation of metastasis.

            Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.
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              The distribution of secondary growths in cancer of the breast. 1889.

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                Author and article information

                Contributors
                ahmed.ahmed@wrh.ox.ac.uk
                Journal
                Oncogene
                Oncogene
                Oncogene
                Nature Publishing Group UK (London )
                0950-9232
                1476-5594
                19 December 2018
                19 December 2018
                2019
                : 38
                : 16
                : 2885-2898
                Affiliations
                [1 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, , University of Oxford, ; Headington, Oxford OX3 9DS UK
                [2 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Nuffield Department of Women’s and Reproductive Health, Women’s Centre, John Radcliffe Hospital, , University of Oxford, ; Headington, Oxford OX3 9DU UK
                [3 ]ISNI 0000 0001 0660 6749, GRID grid.274841.c, Faculty of Life Sciences, Department of Obstetrics and Gynecology, , Kumamoto University, ; 1-1-1 Honjo, Chuo-ku, Kumamoto City, Kumamoto, 860-8556 Japan
                [4 ]ISNI 0000 0004 1936 9959, GRID grid.26091.3c, Division of Gene Regulation, Institute for Advanced Medical Research, , Keio University School of Medicine, ; 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582 Japan
                Author information
                http://orcid.org/0000-0002-8393-8314
                http://orcid.org/0000-0001-6610-1902
                Article
                637
                10.1038/s41388-018-0637-x
                6755962
                30568223
                4e9c91c0-c5d9-4083-a65d-7201de0c11ba
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 September 2018
                : 16 November 2018
                : 19 November 2018
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2019

                Oncology & Radiotherapy
                ovarian cancer,cancer microenvironment
                Oncology & Radiotherapy
                ovarian cancer, cancer microenvironment

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