The expression of five different claudins in invasive breast carcinomas: Comparison of pT1pN1 and pT1pN0 tumors

Tőkés, Anna Mária; Kulka, Janina; Paku, Sándor; Máthé, Miklós; Páska, Csilla; Lódi, Csaba; Kiss, András; Schaff, Zsuzsa

doi:10.1016/j.prp.2005.05.005

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…Some studies have proved that claudin expression and/or claudin expression profile is related to a certain stage of carcinogenesis (uterine cervix) or to a certain subtype of carcinoma (endometrium, ovarium) [13,14]. Rather surprisingly, the attempt to find a link between claudin expression profile and presence or absence of lymph node metastasis in breast cancer cases has been so far unsuccessful [10,11]. The present study revealed different CLDN4 protein expression levels between the basal-like and non-basal grade 3 tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The CLDNs, as a tight junction protein family, consist of 24 known members in humans [9]. According to our previous studies, CLDN4 is related to cellular differentiation [10,11]. The aim of the present study was to explore the possible differences in CLDN4 expression between grade 3 basal-like and grade 1, 2 and grade 3 but not basal-like invasive breast carcinomas.…”

Section: Introductionmentioning

confidence: 94%

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Expression of Tight Junction Protein Claudin-4 in Basal-Like Breast Carcinomas

Kulka

Szász

Németh

et al. 2008

Pathol. Oncol. Res.

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Claudins (CLDN) are tight junction proteins which contribute to the paracellular transport and ionic permeability of various epithelia. In recent years they came into focus for their suggested role in carcinogenesis and possible role in cancer therapy. According to our previous studies, in breast tissue CLDN4 is also related to the level of cellular differentiation. Thirty-eight estrogen (ER) and progesterone receptor (PgR) negative, HER2/neu negative, but cytokeratin 5/6 positive basal-like-mainly grade 3-breast carcinomas were compared with twenty-one grade 1, twenty-five grade 2 and twenty grade 3 non-basal-like invasive breast carcinomas, in respect to their CLDN4 expression. The immunohistochemical reactions were evaluated both semiquantitatively and by morphometrical analysis. Statistically significant difference (p = 0.001) was observable regarding CLDN4 expression in the basal-like group as compared to grade 1 and 2 cancers. Further, CLDN4 expression was significantly higher (p = 0.017) in the basal-like compared with the non-basal-like grade 3 carcinomas. Our results suggest that basal-like carcinomas are a subset of breast cancer with high level of CLDN4 protein expression. The finding is in accordance with our former observation that CLDN4 is indeed related to cellular differentiation. This observation may be seen as a further proof that basal-like carcinomas represent a separable group amongst grade 3 breast carcinomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Expression of Tight Junction Protein Claudin-4 in Basal-Like Breast Carcinomas

Kulka

Szász

Németh

et al. 2008

Pathol. Oncol. Res.

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“…Specifically, Tokés et al (5) reported a decrease in claudin-1 protein expression in 80% of invasive ductal breast carcinomas. In addition, claudin-7 expression has been shown to decrease with increasing breast tumor grade (6,7). These studies indicate that deregulated levels of a number of claudin proteins may contribute to breast tumorigenesis.…”

Section: Introductionmentioning

confidence: 88%

Overexpression and delocalization of claudin-3 protein in MCF-7 and MDA-MB-415 breast cancer cell lines

et al. 2015

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Abstract. Tumor-specific deregulated expression of claudins, integral membrane proteins found in tight junctions (TJs), has indicated a possible role for TJ disruption in cancer progression. The current study demonstrates the marked overexpression of claudin-3 protein in two breast cancer cell lines of metastatic origin (MCF-7 and MDA-MB-415). Immunofluorescence and differential detergent fractionation analyses revealed that, although claudin-3 was primarily localized at cell junctions, it was also detected intracellularly. Similarly, the siRNA-mediated suppression of claudin-3 did not considerably affect its pattern of subcellular distribution relative to mock-transfected cells. However, there appeared to be a preferential loss of claudin-3 signal in the cytoskeletal fraction. Wound-healing assays were conducted to assess the effect of endogenous overexpression versus siRNA-mediated suppression of claudin-3 on cellular motility in MCF-7 cells. Suppression of claudin-3 protein levels resulted in a marked decrease in the rate of cellular motility relative to mock-transfected cells. These findings suggest that overexpression of claudin-3 may be important in disrupting TJ integrity and thus contribute to enhanced cellular motility, a key component of tumor progression. IntroductionThe incidence of breast cancer continues to rise worldwide, particularly in the USA where approximately one in eight females will be diagnosed with breast cancer during her lifetime (1). While early stage breast cancer is readily treatable, patients with metastatic disease pose a greater therapeutic challenge and account for the majority of breast cancer-related mortalities. This is largely due to the paucity of knowledge with regard to the underlying molecular mechanisms associated with malignant progression.Regulated cellular proliferation and differentiation are dependent upon functional tight junctions (TJs), and the loss of TJ integrity may be important in cancer development and progression. Located immediately beneath the apical surface of adjacent endothelial and epithelial cells, TJs form an effective barrier to the diffusion of solutes through the paracellular pathway and exhibit ion-selective permeability in a cell type-dependent manner. In association with adherens junctions, TJs have been shown to establish and maintain epithelial cell polarity by preventing the diffusion of membrane proteins and lipids between the apical and basolateral regions of the plasma membrane. Recent studies also suggest that the TJ plaque proteins, located on the cytoplasmic side of the TJ, are important for the integration of signaling molecules that regulate processes including gene transcription, cellular proliferation, differentiation and morphogenesis. This was reviewed by Turksen and Troy (2).Claudins, the predominant integral membrane proteins that form the backbone of TJs, are required for the assembly, barrier and pore functions of vertebrate TJs (2). Deregulated expression of various claudin proteins has been reported in breast cancer; over...

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“…Some studies demonstrate the loss of specific claudins during breast cancer progression, whereas others suggest that overexpression of particular claudins are associated with poor outcome in breast cancer patients (Martin and Jiang, 2009). For example, some breast cancers exhibit a loss of claudin expression, including claudin-1, -2 and -7 (Kominsky et al, 2003;Sauer et al, 2005;Tokes et al, 2005;Kim et al, 2008), whereas claudin-3 and -4 can be overexpressed in human breast cancers, particularly in the triple-negative subtype (Kominsky et al, 2004;Blanchard et al, 2009;Kulka et al, 2009;Lanigan et al, 2009). Although these studies, which are focused on claudin expression in the primary tumor, suggest that specific claudin proteins may fulfill tumor-suppressor or tumor-promoting roles in breast cancer, little is known regarding claudin expression in breast cancer metastases.…”

Section: Introductionmentioning

confidence: 99%

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

et al. 2010

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The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of a 2 b 1 -and a 5 b 1 -integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target a 5 b 1 and a 2 b 1 complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.

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The expression of five different claudins in invasive breast carcinomas: Comparison of pT1pN1 and pT1pN0 tumors

Cited by 16 publications

References 26 publications

Expression of Tight Junction Protein Claudin-4 in Basal-Like Breast Carcinomas

Expression of Tight Junction Protein Claudin-4 in Basal-Like Breast Carcinomas

Overexpression and delocalization of claudin-3 protein in MCF-7 and MDA-MB-415 breast cancer cell lines

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

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