Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids

Journal of Ovarian Research

Maria V Barbolina²  Joanna E Burdette¹  Joelle D Sacks²  Goda G Muralidhar²  Hilal Gurler²  Jia Xie²  Mark Desjardins² 

[1] Medicinal Chemistry and Pharmacognocy, University of Illinois at Chicago, Chicago, IL 60612, USA;Departments of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, PHARM 335, Chicago, IL 60612, USA

关键词: Migration;    Adhesion;    Versican;    Metastasis;    Ovarian carcinoma;   

Others  :  800810
DOI  :  10.1186/1757-2215-7-70

 received in 2014-02-20, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Desjardins et al.; licensee BioMed Central Ltd.

【 图 表 】

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