Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

Tsutsumi, Kosuke; Sato, Norihiro; Chen, Lin; Mizumoto, Kazuhiro; Sadakari, Yoshihiko; Fujita, Hayato; Ohuchida, Kenoki; Ohtsuka, Takao; Takahata, Shunichi; Tanaka, Masao

doi:10.1038/modpathol.2010.218

Cited by 19 publications

(14 citation statements)

References 28 publications

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“… 91 Consistent with these in vitro findings is a report that claudin-4 expression in pancreatic intraductal papillary mucinous neoplasms was associated with a more invasive phenotype. 92 Similarly, expression of claudin-3 and -4 was observed in advanced ovarian cancer but not in ovarian cystadenomas. 93 , 94 It has been reported, however, that re-expression of claudin-1 in breast cancer cells can lead to the increased apoptosis in three-dimensional cultures.…”

Section: Role Of Claudins and Tight Junctions In Cancermentioning

confidence: 96%

The claudin family of proteins in human malignancy: a clinical perspective

Ding¹,

Lü²,

Lü³

et al. 2013

CMAR

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Tight junctions, or zonula occludens, are the most apical component of the junctional complex and provide one form of cell–cell adhesion in epithelial and endothelial cells. Nearly 90% of malignant tumors are derived from the epithelium. Loss of cell–cell adhesion is one of the steps in the progression of cancer to metastasis. At least three main tight junction family proteins have been discovered: occludin, claudin, and junctional adhesion molecule (JAM). Claudins are the most important structural and functional components of tight junction integral membrane proteins, with at least 24 members in mammals. They are crucial for the paracellular flux of ions and small molecules. Overexpression or downregulation of claudins is frequently observed in epithelial-derived cancers. However, molecular mechanisms by which claudins affect tumorigenesis remain largely unknown. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies, including pancreatic, colonic, lung, ovarian, thyroid, prostate, esophageal, and breast cancers. In this review, we will give the readers an overall picture of the changes in claudin expression observed in various cancers and their mechanisms of regulation. Downregulation of claudins contributes to epithelial transformation by increasing the paracellular permeability of nutrients and growth factors to cancerous cells. In the cases of upregulation of claudin expression, the barrier function of the cancerous epithelia changes, as they often display a disorganized arrangement of tight junction strands with increased permeability to paracellular markers. Finally, we will summarize the literature suggesting that claudins may become useful biomarkers for cancer detection and diagnosis as well as possible therapeutic targets for cancer treatment.

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Section: Role Of Claudins and Tight Junctions In Cancermentioning

confidence: 96%

The claudin family of proteins in human malignancy: a clinical perspective

Ding¹,

Lü²,

Lü³

et al. 2013

CMAR

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“…Several studies have suggested that different clinical characteristics and distinct pathways to malignant progression exist among the various IPMN subtypes. Genetic alteration such as mutational status of GNAS or KRAS [ 42 – 44 ], as well as expression pattern of mucin [ 42 , 43 , 45 , 46 ] have been investigated. Recent meta-analysis suggested that subtype identification should be considered in future guidelines for management of IPMN, since subtypes have an impact on disease prognosis [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of E-cadherin and ZEB1 expression in intraductal papillary mucinous neoplasm

Chang

Park

et al. 2017

Oncotarget

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There is an urgent need to investigate the genetic changes that occur in intraductal papillary mucinous neoplasm (IPMN), which is a well-known precursor of pancreatic cancer. In this study, gene expression profiling was performed by removing unwanted variation to determine the differentially expressed genes (DEGs) associated with malignant progression of IPMN. Among the identified DEGs, zinc finger E-box binding homeobox 1 (ZEB1) and E-cadherin, a crucial regulator of epithelial-to-mesenchymal transition (EMT), was validated among identified DEGs.A total of 76 fresh-frozen tissues were used for gene expression profiling and formalin-fixed, paraffin-embedded blocks from 87 patients were obtained for immunohistochemical analysis. Loss of E-cadherin expression (p = 0.023, odd ratio [OR] = 4.923) and expression of ZEB1 in stromal cells (stromal ZEB1, p < 0.001, OR = 26.800) were significantly correlated with degree of dysplasia. The hazard of death was significantly increased in patients with loss of E-cadherin expression (hazard ratio [HR] = 13.718, p = 0.004), expression of epithelial ZEB1 (HR = 19.117, p = 0.001), and stromal ZEB1 (HR = 6.373, p = 0.043).Based on the results of this study, loss of E-cadherin and expression of stromal ZEB1 are associated with increased risk of malignant progression. Epithelial and stromal ZEB1, as well as E-cadherin may be strong predictors of survival in patients with IPMN. Our finding suggests that these EMT markers may be utilized as potential prognosticators and may be used to improve and personalize treatment of IPMN.

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“…39 Briefly, FFPE samples were cut into 10-Hm sections. One section was stained with hematoxylin-eosin for histological examination, and the number of sections needed for miR extraction was determined according to the estimated area of the neoplastic cells on hematoxylin-eosin staining.…”

Section: Macrodissection and Mir Extraction From Ffpe Samplesmentioning

confidence: 99%