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  • Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells

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    Author(s)
    Choi, Pui-Wah
    Yang, Junzheng
    Ng, Shu-Kay
    Feltmate, Colleen
    Muto, Michael G
    Hasselblatt, Kathleen
    Lafferty-Whyte, Kyle
    JeBailey, Lellean
    MacConaill, Laura
    Welch, William R
    Fong, Wing-Ping
    Berkowitz, Ross S
    Ng, Shu-Wing
    Griffith University Author(s)
    Ng, Shu Kay Angus
    Year published
    2016
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    Abstract
    Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst ...
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    Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst structures were positioned in a stromal-like collagen I matrix. The molecular markers identified in the in vitro 3D models were verified in clinical samples. Network analysis of gene expression of the 3D structures indicates concurrent downregulation of transforming growth factor beta pathway genes and high levels of E-cadherin and microRNA200 (miR200) expression in the cancerous cysts and the migrating cancer cells. Transient silencing of E-cadherin expression in ovarian cancer cells disrupted cyst structures and inhibited collective cell migration. Taken together, our studies employing 3D models have shown that E-cadherin is crucial for ovarian inclusion cyst formation and collective cancer cell migration.
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    Journal Title
    Oncotarget
    Volume
    7
    Issue
    4
    DOI
    https://doi.org/10.18632/oncotarget.6588
    Copyright Statement
    © The Author(s) 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Oncology and Carcinogenesis not elsewhere classified
    Oncology and Carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/142500
    Collection
    • Journal articles

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