title: Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids.
abstract: BACKGROUND
  Epithelial ovarian carcinoma is a deadly disease characterized by overt peritoneal metastasis. Individual cells and multicellular aggregates, or spheroids, seed these metastases, both commonly found in ascites. Mechanisms that foster spheroid attachment to the peritoneal tissues preceding formation of secondary lesions are largely unknown.
  
  
  METHODS
  Cell culture models of SKOV-3, OVCAR3, OVCAR4, Caov-3, IGROV-1, and A2780 were used. In this report the role of versican was examined in adhesion of EOC spheroids and cells to peritoneal mesothelial cell monolayers in vitro as well as in formation of peritoneal tumors using an in vivo xenograft mouse model.
  
  
  RESULTS
  The data demonstrate that versican is instrumental in facilitating cell and spheroid adhesion to the mesothelial cell monolayers, as its reduction with specific shRNAs led to decreased adhesion. Furthermore, spheroids with reduced expression of versican failed to disaggregate to complete monolayers when seeded atop monolayers of peritoneal mesothelial cells. Failure of spheroids lacking versican to disaggregate as efficiently as controls could be attributed to a reduced cell migration that was observed in the absence of versican expression. Importantly, both spheroids and cells with reduced expression of versican demonstrated significantly impaired ability to generate peritoneal tumors when injected intraperitoneally into athymic nude mice.
  
  
  CONCLUSIONS
  Taken together these data suggest that versican regulates the development of peritoneal metastasis originating from cells and spheroids.
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Desjardins
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Hilal
authors.initials: H
authors.lastname: Gurler
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Goda G
authors.initials: GG
authors.lastname: Muralidhar
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Joelle D
authors.initials: JD
authors.lastname: Sacks
authors.affiliation: Medicinal Chemistry and Pharmacognocy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Burdette
authors.affiliation: Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Barbolina
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
chemical_list: D053675:Versicans
keywords: Adhesion; Metastasis; Migration; Ovarian carcinoma; Versican