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

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

doi:10.3390/ijms12021334

Cited by 33 publications

(25 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ovarian cancer patients, carcinoma cells residing within peritoneal fluids adhere to each other and form multicellular suspended cell clusters (41, 42) (Figure 2A). Similarly in our model, we observed that within a 24-hour period, FNE-m-p53 cells, but not control cells, formed compacted cell clusters in suspension (Figure 2A and Supplemental Figure 2A), raising the possibility that m-p53 expression promotes cell-cell adhesion.…”

Section: Resultsmentioning

confidence: 99%

Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition

et al. 2016

View full text Add to dashboard Cite

High-grade serous ovarian carcinoma (HGS-OvCa) harbors p53 mutations and can originate from the epithelial cell compartment of the fallopian tube fimbriae. From this site, neoplastic cells detach, survive in the peritoneal cavity, and form cellular clusters that intercalate into the mesothelium to form ovarian and peritoneal masses. To examine the contribution of mutant p53 to phenotypic alterations associated with HGS-OvCA, we developed live-cell microscopy assays that recapitulate these early events in cultured fallopian tube nonciliated epithelial (FNE) cells. Expression of stabilizing mutant variants of p53, but not depletion of endogenous wild-type p53, in FNE cells promoted survival and cell-cell aggregation under conditions of cell detachment, leading to the formation of cell clusters with mesothelium-intercalation capacity. Mutant p53R175H-induced phenotypes were dependent on fibronectin production, α5β1 fibronectin receptor engagement, and TWIST1 expression. These results indicate that FNE cells expressing stabilizing p53 mutants acquire anchorage independence and subsequent mesothelial intercalation capacity through a mechanism involving mesenchymal transition and matrix production. These findings provide important new insights into activities of mutant p53 in the cells of origin of HGS-OvCa.

show abstract

Section: Resultsmentioning

confidence: 99%

Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Three-dimensional (3D) systems such as multicellular tumor spheroids better reflect the behavior of cells in tumors and, interestingly, claudins have been implicated in spheroid formation. 36 We therefore used a 3D spheroid ovarian cancer model to test whether claudin-6 could also be used as a receptor under these conditions. Interestingly, multicellular tumor spheroid of UCI-101 cells (which express claudin-6, but not claudin-3 or -4) were sensitive to CPE, demonstrating that spheroid formation did not impede the ability of CPE to interact with claudin-6 and induce cell death.…”

Section: Discussionmentioning

confidence: 99%

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer

2012

View full text Add to dashboard Cite

Claudins are integral tight junction proteins that are responsible for maintaining the integrity of epithelial cell architecture and cell polarity. Claudin-3 and -4 are overexpressed in several cancers and have been shown to act as receptors for the Clostridium perfringens enterotoxin (CPE), a toxin that causes rapid cell lysis. CPE has demonstrated effectiveness in treating several different cancers in mouse models, provided that these cancers express claudin-3 or claudin-4. Here, we show that claudin-3/4 expression is not an absolute requirement for CPE action and, through overexpression and knockdown experiments, we identify claudin-6 as a novel functional receptor for CPE. Indeed, UCI-101, an ovarian cancer cell line highly sensitive to CPE, does not express claudin-3/4 and knockdown of claudin-6 in these cells decreases CPE sensitivity. Moreover, two different ovarian cell lines that are resistant to the effects of CPE can be made sensitive through claudin-6 overexpression. Binding assays show that CPE can indeed bind claudin-6 in cells and that this binding is associated with CPE cytotoxicity. Multicellular tumor spheroids experiments demonstrate that claudin-6 can also be a target of CPE in three-dimensional cultures. Our data establish claudin-6 as a novel receptor for CPE and introduces the possibility of a novel targeted therapeutic for ovarian and other cancers that express claudin-6.

show abstract

“…At a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51 and 71%, respectively, and the two tests were strongly correlated (Li et al, 2009a). Claudin-4 was further shown to be involved in spheroid formation in ovarian carcinoma (Boylan et al, 2011), as well as in angiogenesis (Li et al, 2009b). Claudin-7 was recently shown to promote invasion of ovarian carcinoma cells in vitro , whereas migration was inhibited (Dahiya et al, 2011).…”

Section: Epithelial Markers Targeted By Emtmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in Ovarian Carcinoma

Davidson¹,

Tropé²,

Reich³

2012

Front. Oncol.

140

146

View full text Add to dashboard Cite

Ovarian cancer is the most lethal gynecologic malignancy, with the majority of patients dying within 5 years of diagnosis. This poor survival of patients diagnosed with this malignancy is attributed to diagnosis at advanced stage, when the tumor has metastasized, and to chemotherapy resistance, either primary or developing along tumor progression. However, ovarian carcinomas, constituting the vast majority of ovarian cancers, additionally have unique biology, one aspect of which is the ability to co-express epithelial and mesenchymal determinants. epithelial–mesenchymal transition (EMT), a physiological process by which mesenchymal cells are formed and migrate to target organs during embryogenesis, is involved in cancer cell invasion and metastasis. However, these changes do not fully occur in ovarian carcinoma, and are even reversed in tumor cells present in malignant peritoneal and pleural effusions. This review summarizes current knowledge in this area, including the characteristics of EMT related to adhesion, transcriptional regulation and chemoresistance, and their clinical relevance, as well as the recently observed regulation of EMT by microRNA.

show abstract

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

Cited by 33 publications

References 65 publications

Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition

Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer

Epithelial–Mesenchymal Transition in Ovarian Carcinoma

Contact Info

Product

Resources

About