Reduced Expression of Claudin-2 is Associated with High Histological Grade and Metastasis of Feline Mammary Carcinomas

Flores, Anabel; Rêma, Alexandra; Carvalho, Félix; Faustino, Augusto; Dias‐Pereira, Patrícia

doi:10.1016/j.jcpa.2013.09.004

Cited by 9 publications

(8 citation statements)

References 25 publications

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“…p53 was moderately expressed in all of the pellets evaluated. CLDN-2 was weakly expressed in all pellets (score 1 to 3) 42 . The mean Ki-67 proliferation index of TiHo-0906 cells in pellets was 39.3% and 42.2% in early and high passages, respectively.…”

Section: Resultsmentioning

confidence: 97%

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Granados-Soler

Junginger

Hewicker‐Trautwein

et al. 2018

Sci Rep

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Feline mammary carcinomas (FMCs) with anaplastic and malignant spindle cells histologically resemble the human metaplastic breast carcinoma (hMBC), spindle-cell subtype. hMBCs display epithelial-to-mesenchymal transition (EMT) characteristics. Herein we report the establishment and characterization of a cell line (TiHoCMglAdcar0906; TiHo-0906) exhibiting EMT-like properties derived from an FMC with anaplastic and malignant spindle cells. Copy-number variations (CNVs) by next-generation sequencing and immunohistochemical characteristics of the cell line and the tumour were compared. The absolute qPCR expression of EMT-related markers HMGA2 and CD44 was determined. The growth, migration, and sensitivity to doxorubicin were assessed. TiHo-0906 CNVs affect several genomic regions harbouring known EMT-, breast cancer-, and hMBCs-associated genes as AKT1, GATA3, CCND2, CDK4, ZEB1, KRAS, HMGA2, ESRP1, MTDH, YWHAZ, and MYC. Most of them were located in amplified regions of feline chromosomes (FCAs) B4 and F2. TiHo-0906 cells displayed an epithelial/mesenchymal phenotype, and high HMGA2 and CD44 expression. Growth and migration remained comparable during subculturing. Low-passaged cells were two-fold more resistant to doxorubicin than high-passaged cells (IC50: 99.97 nM, and 41.22 nM, respectively). The TiHo-0906 cell line was derived from a poorly differentiated cellular subpopulation of the tumour consistently displaying EMT traits. The cell line presents excellent opportunities for studying EMT on FMCs.

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Section: Resultsmentioning

confidence: 97%

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Granados-Soler

Junginger

Hewicker‐Trautwein

et al. 2018

Sci Rep

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“…Although not on a human scale, progress has been made in respect to the feline mammary tumors’ expression profile and proteins’ repertoire. The expression profiling of the following genes transcripts or proteins has been conducted in FMCs over the last 17 years ( Table 1 ), namely: BCL-2 [ 76 ], p53 [ 77 ], Cyclin A (apparently not overexpressed in feline mammary tumors [ 51 ]), Mst1R [ 48 ], ER [ 50 , 78 ], erbB-2 [ 2 , 41 , 63 , 78 , 79 ], COX-2 [ 80 ], Pten [ 75 , 81 ], Akt [ 82 ], mTOR [ 83 ], CXCR4 [ 84 ], catenins [ 85 ], cadherins [ 85 , 86 ], Twist-1 [ 49 ], claudins, CLDNs [ 87 , 88 ], Notch1 [ 89 ], PR, CK5/6 [ 78 ] or Ki-67 [ 78 , 90 ].…”

Section: Cat Critical Cancer Genes: From Gene Expression Patterns mentioning

confidence: 99%

“…Claudins (CLDNs) are tight junction proteins involved in cell adhesion and polarity, paracellular permeability, proliferation and differentiation [ 87 , 88 ]. Several studies showed reduced expression of claudins in human (and canine mammary carcinomas) (e.g., [ 126 , 127 , 128 ]), suggesting that the decrease in these proteins contribute to mammary carcinogenesis, invasion and metastasis (e.g., [ 129 , 130 ]).…”

Section: Cat Critical Cancer Genes: From Gene Expression Patterns mentioning

confidence: 99%

“…Several studies showed reduced expression of claudins in human (and canine mammary carcinomas) (e.g., [ 126 , 127 , 128 ]), suggesting that the decrease in these proteins contribute to mammary carcinogenesis, invasion and metastasis (e.g., [ 129 , 130 ]). Flores et al [ 87 , 88 ] suggested that the evaluation of expression of CLDN-7 and CLDN-2 may be of prognostic and diagnostic value, specifically in a subgroup of aggressive FMCs that share some features with the recently characterized “claudin-low” subgroup of human breast cancer [ 131 , 132 ].…”

Section: Cat Critical Cancer Genes: From Gene Expression Patterns mentioning

confidence: 99%

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Cat Mammary Tumors: Genetic Models for the Human Counterpart

Adega

Borges

Chaves

2016

Veterinary Sciences

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The records are not clear, but Man has been sheltering the cat inside his home for over 12,000 years. The close proximity of this companion animal, however, goes beyond sharing the same roof; it extends to the great similarity found at the cellular and molecular levels. Researchers have found a striking resemblance between subtypes of feline mammary tumors and their human counterparts that goes from the genes to the pathways involved in cancer initiation and progression. Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and neoplasias) and malignant lesions seem to share a wide repertoire of molecular features with their human counterparts. In the present review, we tried to compile all the genetics aspects published (i.e., chromosomal alterations, critical cancer genes and their expression) regarding cat mammary tumors, which support the cat as a valuable alternative in vitro cell and animal model (i.e., cat mammary cell lines and the spontaneous tumors, respectively), but also to present a critical point of view of some of the issues that really need to be investigated in future research.

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“…Claudin-2 is expressed in the small intestine and the proximal tubules of kidney under physiological conditions and con-trols monovalent cation permeability (31,32). The elevation of claudin-2 expression has been reported in colorectal (16), fibrolamellar hepatocellular (33), and gastric cancers (34), whereas reduced expression of claudin-2 is associated with a high histological grade and metastasis of feline mammary carcinomas (35). We recently found that claudin-2 is highly expressed in human lung adenocarcinoma tissues and cultured cells, although it is absent in normal lung tissues (10).…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of Claudin-2 Expression and Proliferation by Epigenetic Inhibitors in Human Lung Adenocarcinoma A549 Cells

Hichino

Okamoto

Taga

et al. 2017

Journal of Biological Chemistry

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Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases proliferation in adenocarcinoma cells. The chemicals that reduce claudin-2 expression may have anti-cancer effects, but such therapeutic medicines have not been developed. We found that azacitidine (AZA), a DNA methylation inhibitor, and trichostatin A (TSA) and sodium butyrate (NaB), histone deacetylase (HDAC) inhibitors, decrease claudin-2 levels. The effect of AZA was mediated by the inhibition of phosphorylated Akt and NF-κB. LY-294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and BAY 11-7082, an NF-κB inhibitor, decreased claudin-2 levels. The reporter activity of claudin-2 was decreased by AZA and LY-294002, which was blocked by the mutation in a putative NF-κB-binding site. NF-κB bound to the promoter region of claudin-2, which was inhibited by AZA and LY-294002. AZA is suggested to decrease the claudin-2 mRNA level mediated by the inhibition of a PI3K/Akt/NF-κB pathway. TSA and NaB did not change phosphorylated Akt and NF-κB levels. Furthermore, these inhibitors did not change the reporter activity of claudin-2 but decreased the stability of claudin-2 mRNA mediated by the elevation of miR-497 microRNA. The binding of histone H3 to the promoter region of miR-497 was inhibited by TSA and NaB, whereas that of claudin-2 was not. These results suggest that HDAC inhibitors decrease claudin-2 levels mediated by the elevation of miR-497 expression. Cell proliferation was additively decreased by AZA, TSA, and NaB, which was partially rescued by ectopic expression of claudin-2. We suggest that epigenetic inhibitors suppress the abnormal proliferation of lung adenocarcinoma cells highly expressing claudin-2.

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Reduced Expression of Claudin-2 is Associated with High Histological Grade and Metastasis of Feline Mammary Carcinomas

Cited by 9 publications

References 25 publications

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Cat Mammary Tumors: Genetic Models for the Human Counterpart

Down-regulation of Claudin-2 Expression and Proliferation by Epigenetic Inhibitors in Human Lung Adenocarcinoma A549 Cells

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