Claudin 4 Is Differentially Expressed between Ovarian Cancer Subtypes and Plays a Role in Spheroid Formation

International Journal of Molecular Sciences

Kristin L. M. Boylan¹  Benjamin Misemer¹  Melissa S. DeRycke¹  John D. Andersen¹  Katherine M. Harrington¹  Steve E. Kalloger²  C. Blake Gilks²  Stefan E. Pambuccian¹ 

[1] Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA; E-Mails:;Cheryl Brown Ovarian Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, Canada; E-Mails:

关键词: ovarian cancer;    claudin 4;    biomarker;    spheroid;    ascites;   

DOI  :  10.3390/ijms12021334

来源: mdpi

【 摘 要 】

Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients’ ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients’ ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity.

【 授权许可】

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© 2011 by the authors; licensee MDPI, Basel, Switzerland.