• Abstract
• Full-Text PDF [1197 KB]
• Full-Text XML
• Article Versions Notes

• Article Statistics
• PubMed/Medline
• Google Scholar
• Order Reprints

• Cite this article
• Export to BibTeX
• Export to EndNote

• [+] on DOAJ
• Boylan, K
• Misemer, B
• DeRycke, MS.
• Andersen, JD.
• Harrington, KM.
• Kalloger, SE.
• Gilks, C
• Pambuccian, SE.
• Skubitz, AP. N.
• [+] on Google Scholar
• Boylan, K
• Misemer, B
• DeRycke, MS.
• Andersen, JD.
• Harrington, KM.
• Kalloger, SE.
• Gilks, C
• Pambuccian, SE.
• Skubitz, AP. N.
• [+] on PubMed
• Boylan, K
• Misemer, B
• DeRycke, MS.
• Andersen, JD.
• Harrington, KM.
• Kalloger, SE.
• Gilks, C
• Pambuccian, SE.
• Skubitz, AP. N.

•  CiteULike
•  Facebook
•  Mendeley
•  Twitter

This article is

• freely available
• re-usable

Int. J. Mol. Sci. 2011, 12(2), 1334-1358; doi:10.3390/ijms12021334

Article

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

Kristin L. M. Boylan ¹ , Benjamin Misemer ¹ , Melissa S. DeRycke ¹ , John D. Andersen ¹ , Katherine M. Harrington ¹ , Steve E. Kalloger ² , C. Blake Gilks ² , Stefan E. Pambuccian ¹  and Amy P. N. Skubitz ^1,*

¹ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA ² Cheryl Brown Ovarian Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, Canada

* Author to whom correspondence should be addressed.

Received: 17 January 2011; in revised form: 12 February 2011 / Accepted: 12 February 2011 / Published: 22 February 2011

(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer)

Download PDF Full-Text [1197 KB, uploaded 22 February 2011 12:41 CET]

Abstract: 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.

Keywords: ovarian cancer; claudin 4; biomarker; spheroid; ascites

Article Statistics

Cite This Article