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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1334-1358
Number of pages25
JournalInternational journal of molecular sciences
Volume12
Issue number2
DOIs
StatePublished - Jan 1 2011

Fingerprint

Claudin-4
spheroids
Ovarian Neoplasms
cancer
Tissue
Dextran
Microarrays
Tumors
cells
Assays
Adhesion
Cells
Association reactions
Molecules
Ascites
Small Interfering RNA
dextrans
staining
Cellular Spheroids
exclusion

Keywords

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

Cite this

Claudin 4 is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation. / Boylan, Kristin L; Misemer, Benjamin; DeRycke, Melissa S.; Andersen, John D.; Harrington, Katherine M.; Kalloger, Steve E.; Gilks, C. Blake; Pambuccian, Stefan E.; Skubitz, Amy P.

In: International journal of molecular sciences, Vol. 12, No. 2, 01.01.2011, p. 1334-1358.

Research output: Contribution to journalArticle

Boylan, Kristin L ; Misemer, Benjamin ; DeRycke, Melissa S. ; Andersen, John D. ; Harrington, Katherine M. ; Kalloger, Steve E. ; Gilks, C. Blake ; Pambuccian, Stefan E. ; Skubitz, Amy P. / Claudin 4 is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation. In: International journal of molecular sciences. 2011 ; Vol. 12, No. 2. pp. 1334-1358.
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