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

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 ovari...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826193/
https://www.ncbi.nlm.nih.gov/pubmed/26684027
http://dx.doi.org/10.18632/oncotarget.6588
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author 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
author_facet 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
author_sort Choi, Pui-Wah
collection PubMed
description 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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spelling pubmed-48261932016-05-09 Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells 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 Oncotarget Research Paper 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. Impact Journals LLC 2015-12-13 /pmc/articles/PMC4826193/ /pubmed/26684027 http://dx.doi.org/10.18632/oncotarget.6588 Text en Copyright: © 2016 Choi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
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
Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title_full Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title_fullStr Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title_full_unstemmed Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title_short Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
title_sort loss of e-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826193/
https://www.ncbi.nlm.nih.gov/pubmed/26684027
http://dx.doi.org/10.18632/oncotarget.6588
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