title: Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells.
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 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.
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.|Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Pui-Wah
authors.initials: PW
authors.lastname: Choi
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Junzheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Medicine, Griffith University, Meadowbrook, Australia.
authors.forename: Shu-Kay
authors.initials: SK
authors.lastname: Ng
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Feltmate
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Muto
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hasselblatt
authors.affiliation: GeneGo, Thomson Reuters, New York, New York, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Lafferty-Whyte
authors.affiliation: GeneGo, Thomson Reuters, New York, New York, USA.
authors.forename: Lellean
authors.initials: L
authors.lastname: JeBailey
authors.affiliation: Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: MacConaill
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Welch
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wing-Ping
authors.initials: WP
authors.lastname: Fong
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Ross S
authors.initials: RS
authors.lastname: Berkowitz
authors.affiliation: Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Shu-Wing
authors.initials: SW
authors.lastname: Ng
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008856:Microscopy, Fluorescence; D010048:Ovarian Cysts / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger
keywords: collective movement; inclusion cyst; ovarian cancer; three-dimensional culture; tumor invasion