Claudin 1 Expression Characterizes Human Uterine Cervical Reserve Cells

Zinner, Balázs; Gyöngyösi, Benedek; Babarczi, Edit; Kiss, András; Sobel, Gábor

doi:10.1369/0022155413501324

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…On the other hand, the expression of claudin-1 was reduced compared with that in the rest of the cervix in the invasive papillomas that developed in 7-month-old K14E7 mice treated with E 2 . These results are consistent with previous research which shows that claudin-1 is markedly expressed in grades I, II and III of human intraepithelial neoplasias, and in situ carcinomas ( 53 - 55 ), but decreases with progression to the invasive phenotype ( 56 ).…”

Section: Discussionsupporting

confidence: 93%

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Uc¹,

Miranda²,

Raya‐Sandino³

et al. 2020

Int J Oncol

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Tight junctions (TJs) are cell-cell adhesion structures frequently altered by oncogenic transformation. In the present study the role of human papillomavirus (HPV) 16 E7 oncoprotein on the sealing of TJs was investigated and also the expression level of claudins in mouse cervix and in epithelial Madin-Darby Canine Kidney (MDCK) cells. It was found that there was reduced expression of claudins-1 and-10 in the cervix of 7-month-old transgenic K14E7 mice treated with 17β-estradiol (E 2), with invasive cancer. In addition, there was also a transient increase in claudin-1 expression in the cervix of 2-month-old K14E7 mice, and claudin-10 accumulated at the border of cells in the upper layer of the cervix in FvB mice treated with E 2 , and in K14E7 mice treated with or without E 2. These changes were accompanied by an augmented paracellular permeability of the cervix in 2-and 7-month-old FvB mice treated with E 2 , which became more pronounced in K14E7 mice treated with or without E 2. In MDCK cells the stable expression of E7 increased the space between adjacent cells and altered the architecture of the monolayers, induced the development of an acute peak of transepithelial electrical resistance accompanied by a reduced expression of claudins-1,-2 and-10, and an increase in claudin-4. Moreover, E7 enhances the ability of MDCK cells to migrate through a 3D matrix and induces cell stiffening and stress fiber formation. These observations revealed that cell transformation induced by HPV16 E7 oncoprotein was accompanied by changes in the pattern of expression of claudins and the degree of sealing of epithelial TJs.

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Section: Discussionsupporting

confidence: 93%

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Uc¹,

Miranda²,

Raya‐Sandino³

et al. 2020

Int J Oncol

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“…Although a specific marker for reserve cells has yet to be identified [ 22 – 27 ], we considered p63, CK5 and CK8 as reserve cell markers because they serve as markers for basal stem cells, primary squamous cells and primary glandular cells, respectively. We first investigated a method to induce populations highly expressing p63 because p63 is known to be essential for the stemness of the epithelium in the basal layers [ 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…One limitation of our study was that we did not have any positive controls for the reserve cells. Because there is no definition for reserve cells, for example, in terms of gene expression patterns or gene expression levels, we could not demonstrate that the properties we induced were really reserve cells [ 10 , 22 – 24 , 27 ]. However, we showed a new approach for cervical CSC research, and in that sense, we can conclude that iRCs are potentially useful.…”

Section: Discussionmentioning

confidence: 98%

Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment

et al. 2017

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Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.

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“…On the other hand, Biswas et al and Zinner et al reported that claudin-1 is mainly expressed near the basal layer region and co-stained with Tp63 in epithelial cells. 19,20 Additionally, Chang et al demonstrated that claudin-1 acts as an oncogene in cancer, driving oncogenesis and regulates proliferation in the head and neck squamous cell carcinoma. 21 We found claudin-1 was significantly up-regulated with basal cells' excessive proliferation, which suggests claudin-1 is possibly involved in the mechanism of epithelial cells' aberrant proliferation in NIP.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent study has observed that claudin‐3 is predominantly localized in ciliated cells in vitro, 8 implying that the down‐regulation of claudin‐3 may be caused by the inhibition of ciliated cell differentiation in NIP. On the other hand, Biswas et al and Zinner et al reported that claudin‐1 is mainly expressed near the basal layer region and co‐stained with Tp63 in epithelial cells 19,20 . Additionally, Chang et al demonstrated that claudin‐1 acts as an oncogene in cancer, driving oncogenesis and regulates proliferation in the head and neck squamous cell carcinoma 21 .…”

Section: Discussionmentioning

confidence: 99%

Epithelial Tight Junction Anomalies in Nasal Inverted Papilloma

et al. 2023

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ObjectivesAs a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP.MethodsWe assessed the expression of ZO‐1, occludin, claudin‐1, claudin‐3, and claudin‐7 in healthy controls and NIP by real‐time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, TH1/TH2/TH17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated.ResultsUpregulation of ZO‐1, occludin, claudin‐1, and claudin‐7, along with downregulation of claudin‐3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin‐3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO‐1, but positively with claudin‐3 (all p < 0.05). Furthermore, FOXP3, IL‐10, TGF‐β1, IL‐5, IL‐13, and IL‐22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL‐10, IL‐5, IL‐13, and IL‐22, whereas ZO‐1 was positively with TGF‐β1 (all p < 0.05).ConclusionNasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP.Level of EvidenceNA Laryngoscope, 2023

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Claudin 1 Expression Characterizes Human Uterine Cervical Reserve Cells

Cited by 9 publications

References 25 publications

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment

Epithelial Tight Junction Anomalies in Nasal Inverted Papilloma

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