Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation

Sherwood, Amanda R.; Mutsaers, Steve; Peeva, Violet K.; Robinson, Cleo; Desilva, Chitra; Swanson, Nigel; Lake, Richard

doi:10.1111/j.1365-2184.2008.00560.x

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…The most used immortalized human mesothelial cell lines are MeT-5A immortalized with SV40 (Ke et al 1989 ) and LP9 cells immortalized with TERT1, the catalytic component of telomerase (Connell and Rheinwald 1983 ). Immortalized mesothelioma and mesothelial cells of mouse origin include cells isolated from the ascites of asbestos-exposed wild-type C57Bl/6J or BALB/c mice [40, 40L, AE17, AK7 (Cordier Kellerman et al 2003 ), and AB12 (Davis et al 1992 )], SV40 TAg transgenic mice [MexTAg, line names TGM299h, TGM304i, TGM270i, and TGM266i (Robinson et al 2006 ), conditional Nf2−/− mice (Jongsma et al 2008 )], and spontaneously immortalized cells obtained after prolonged culturing of primary mouse mesothelial cells (Sherwood et al 2008 ). Here, we established SV40-immortalized mesothelial cells of WT mice and immortalized cells derived from (Nf2+/−) mice; all lines stem from mesothelial cells isolated from mice with C57Bl/6J background.…”

Section: Introductionmentioning

confidence: 99%

Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line

Blum

Pecze

Felley‐Bosco

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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Mesothelial cells are susceptible to asbestos fiber-induced cytotoxicity and on longer time scales to transformation; the resulting mesothelioma is a highly aggressive neoplasm that is considered as incurable at the present time Zucali et al. (Cancer Treatment Reviews 37:543–558, 2011). Only few murine cell culture models of immortalized mesothelial cells and mesothelioma cell lines exist to date. We generated SV40-immortalized cell lines derived from wild-type (WT) and neurofibromatosis 2 (merlin) heterozygote (Nf2+/−) mice, both on a commonly used genetic background, C57Bl/6J. All immortalized mesothelial clones consistently grow in DMEM supplemented with fetal bovine serum. Cells can be passaged for more than 40 times without any signs of morphological changes or a decrease in proliferation rate. The tumor suppressor gene NF2 is one of the most frequently mutated genes in human mesothelioma, but its detailed function is still unknown. Thus, these genotypically distinct cell lines likely relevant for malignant mesothelioma formation are expected to serve as useful in vitro models, in particular to compare with in vivo studies in mice of the same genotype. Furthermore, we generated a novel murine mesothelioma cell line RN5 originating from an Nf2+/− mouse subjected to repeated crocidolite exposure. RN5 cells are highly tumorigenic.

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Section: Introductionmentioning

confidence: 99%

Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line

Blum

Pecze

Felley‐Bosco

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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“…Washed cells were resuspended in PBS/5% FCS and analysed on a FACScan analyser (Becton Dickinson, Franklin Lakes, NJ, USA). Cells were also characterized ultrastructurally by transmission electron microscopy (TEM) using standard techniques [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Mesothelial cell differentiation into osteoblast‐ and adipocyte‐like cells

Lansley¹,

Searles²,

Hoi³

et al. 2011

J Cellular Molecular Medi

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Serosal pathologies including malignant mesothelioma (MM) can show features of osseous and/or cartilaginous differentiation although the mechanism for its formation is unknown. Mesothelial cells have the capacity to differentiate into cells with myofibroblast, smooth muscle and endothelial cell characteristics. Whether they can differentiate into other cell types is unclear. This study tests the hypothesis that mesothelial cells can differentiate into cell lineages of the embryonic mesoderm including osteoblasts and adipocytes. To examine this, a functional assay of bone formation and an adipogenic assay were performed in vitro with primary rat and human mesothelial cells maintained in osteogenic or adipogenic medium (AM) for 0–26 days. Mesothelial cells expressed increasing levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and formed mineralized bone-like nodules. Mesothelial cells also accumulated lipid indicative of a mature adipocyte phenotype when cultured in AM. All cells expressed several key osteoblast and adipocyte markers, including osteoblast-specific runt-related transcription factor 2, and demonstrated changes in mRNA expression consistent with epithelial-to-mesenchymal transition. In conclusion, these studies confirm that mesothelial cells have the capacity to differentiate into osteoblast- and adipocyte-like cells, providing definitive evidence of their multipotential nature. These data strongly support mesothelial cell differentiation as the potential source of different tissue types in MM tumours and other serosal pathologies, and add support for the use of mesothelial cells in regenerative therapies.

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“…2009). For example, Sherwood et al. (2008) reported that a spontaneously immortalized mouse cell line displayed characteristics of malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

“…The cells appear to be unsuitable for research on the functions and mechanisms of normal mammary gland cells, because of genomic aberration, cellular heterogeneity and malignancy (Yamasaki et al 2009). For example, Sherwood et al (2008) reported that a spontaneously immortalized mouse cell line displayed characteristics of malignant transformation. Furthermore, like the c-Myc and SV40-immortalized cell lines, these cells underwent modifications of many tumor-related genes, which led to aberrant protein expression (Guerreiro Da Silva et al 2000;Esteban et al 2003;Thibodeaux et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Recombinant adenovirus‐mediated human telomerase reverse transcriptase gene can stimulate cell proliferation and maintain primitive characteristics in bovine mammary gland epithelial cells

Zheng

Lan

et al. 2011

Dev Growth Differ

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The human telomerase reverse transcriptase (hTERT) gene has been used to stimulate the proliferation of most types of human cells. The present study was designed to evaluate the feasibility and efficiency of adenovirusmediated hTERT in the proliferation of bovine mammary gland epithelial cells (bMGEs). A plasmid and an adenovirus vector that carried hTERT, namely pEGFP-hTERT and Ad-hTERT, were constructed and transfected into bMGEs, respectively. In order to select the best strategy for stimulating cell proliferation, the adenovirusand plasmid-mediated hTERT were compared in terms of the positive cloning and transgenic efficiency. The results showed that only Ad-hTERT had high infection efficiency and produced a positive polyclone population (hTERT-bMGEs). The characteristics of the hTERT-bMGEs were investigated with further analysis by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, proliferation assays, and flow cytometry, which showed that hTERT facilitated strong cell proliferation. Real-time quantitative PCR showed a normal level of expression of beta-casein, the caspase-8 and c-myc proto-oncogene, and immunofluorescence demonstrated the properties of the epithelial cells. In conclusion, the adenovirus-mediated hTERT gene could not only extend the cell lifespan, but also maintained the primary characteristics of the cells. It may be possible to extend the use of a wide variety of non-human mammalian cells in this way. This study has provided additional insight into the mechanism of cell proliferation by demonstrating the lack of integration of the adenovirus-mediated hTERT gene into the mammalian genome.

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Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation

Abstract: These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.

Cited by 7 publications

References 27 publications

Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line

Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line

Mesothelial cell differentiation into osteoblast‐ and adipocyte‐like cells

Recombinant adenovirus‐mediated human telomerase reverse transcriptase gene can stimulate cell proliferation and maintain primitive characteristics in bovine mammary gland epithelial cells

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