Claudin 4 is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation

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

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1334-1358
Number of pages25
JournalInternational journal of molecular sciences
Issue number2
StatePublished - Feb 2011


  • Ascites
  • Biomarker
  • Claudin 4
  • Ovarian cancer
  • Spheroid


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