The Analysis of Malignancy by Cell Fusion

1971 ◽  
Vol 8 (3) ◽  
pp. 659-672
Author(s):  
G. KLEIN ◽  
U. BREGULA ◽  
F. WIENER ◽  
H. HARRIS
Keyword(s):  
Cell Line ◽  
Tumour Cell ◽  
Malignant Cell ◽  
Hybrid Cells ◽  
Metabolic Defects ◽  
L Cell ◽  
Wide Range ◽  
Derivatives Of ◽  
Selection Of

A wide range of different kinds of malignant cell were fused with certain derivatives of the L cell line and the ability of the resulting hybrid cells to grow progressively in vivo was examined. In all cases the highly malignant character of the tumour cells was suppressed by fusion with the L cell derivatives, whether or not these had metabolic defects that facilitated selection of the hybrid cells. So long as the hybrid cells retained the complete chromosome complements of the two parent cells, their ability to grow progressively in vivo was very limited, for tumours composed of such unreduced hybrids were not found. However, when they lost certain specific, but as yet unidentified, chromosomes, the hybrid cells regained the ability to grow progressively in vivo and gave rise to a tumour. These findings thus indicated that the L cell derivatives contributed something to the hybrid that suppressed the malignancy of the tumour cell, and that this contribution was lost when certain specific chromosomes were eliminated.

The Analysis of Malignancy by Cell Fusion

1973 ◽  
Vol 12 (1) ◽  
pp. 253-261
Author(s):  
F. WIENER ◽  
G. KLEIN ◽  
H. HARRIS
Keyword(s):  
Tumour Cell ◽  
Tumour Cells ◽  
Hybrid Cells ◽  
Wild Type ◽  
Malignant Phenotype ◽  
L Cell ◽  
Progressive Growth ◽  
Mouse Tumour ◽  
Derivatives Of

Previous experiments showed that when a range of different highly malignant mouse tumour cells were fused with L cell derivatives of low tumorigenicity, the resulting hybrid cells, so long as they retained something close to the complete chromosome sets of both parent cells, had little or no ability to grow progressively in vivo. Tumours arising from the injection of such hybrids were produced not by progressive growth of the cells injected, but by selective overgrowth of cells from which certain specific, but as yet unidentified, chromosomes had been eliminated. In the present experiments the same malignant mouse tumour cells were fused with a highly malignant L cell derivative selected from the wild type cell population by passage through the animal. In all cases the resulting hybrid cells were found to be highly malignant; and the chromosome constitutions of the tumours arising from the injection of these hybrids were not significantly different from those of the cells injected. These findings confirm the interpretation given to the previous work; the L cell derivatives of low tumorigenicity contribute to the hybrid cells some factor, linked to specific chromosomes, that suppresses the malignant character of the tumour cell, and this suppression is removed, with consequent reappearance of the malignant phenotype, when certain chromosomes are eliminated.

Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells

1983 ◽  
Vol 62 (1) ◽  
pp. 49-80
Author(s):  
M.K. White ◽  
M.E. Bramwell ◽  
H. Harris
Keyword(s):  
Kinetic Parameters ◽  
Malignant Cell ◽  
Hexose Transport ◽  
Hybrid Cells ◽  
Michaelis Constant ◽  
Independent Measurement ◽  
The Difference ◽  
Hexose Uptake ◽  
Derivatives Of

Matched pairs of isogeneic hybrid cells, in which one member of the pair was malignant and the other not, were used to examine the linkage between malignancy and functional alterations in hexose transport. The kinetic parameters of uptake of 2-deoxy-D-glucose were measured in a range of such hybrids, both human and murine. Some other malignant cell lines were also examined and were compared with non-tumorigenic derivatives of tumour cells selected by exposure to the lectin, wheat-germ agglutinin. In every case, malignancy, as defined by the ability of cells to grow progressively in vivo, was found to be linked to a decrease in the Michaelis constant of hexose uptake. Independent measurement of the transport and phosphorylation reactions involved in hexose uptake revealed that this decrease was determined by the membrane transport system. The difference in Michaelis constant between malignant and non-malignant cells was observed with 3-O-methylglucose, a hexose that is transported into the cell but not further metabolized. The activity of hexokinase in cell homogenates was higher than the level that would be required to cope with transport and showed no correlation with tumorigenicity. Measurement of the uptake of D-glucose itself, by a rapid filtration centrifugation method, gave results similar to those obtained with 2-deoxy-D-glucose.

scholarly journals The influence of chromone based hydrazones on lipid peroxidation and bFGF concentration in the HL-60 cell line.

2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Andrzej Łazarenkow ◽  
Marta Michalska ◽  
Anna Gorąca ◽  
Marek Mirowski ◽  
Jolanta Nawrot-Modranka ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Line ◽  
Significant Influence ◽  
Biological Properties ◽  
Synthetic Analogues ◽  
Wide Range ◽  
Synthetic Derivatives ◽  
Derivatives Of

Natural and synthetic derivatives of benzo-γ-pyrones (i.e. flavones, chromones, and coumarins) and their synthetic analogues possess a wide range of biological properties in vitro and in vivo. In this paper we investigated the influence of two hydrazone compounds of chromones, 3-{[(2-dimethoxytiophosphoryl)-2-methylhydrazono]-methyl}-chromen-4-one (CH-3) and 2-amino-6-chloro-3-[(2-hydroxyethyl)-hydrazonomethyl]-chromen-4-one (A-12), on lipid peroxidation and bFGF concentration in the HL-60 cells. Both of the studied compounds had a significant influence on bFGF and TBARS in ranges -137.20 ~ 380.26% and -81.66 ~ -28.68%, respectively, in comparison with the control (counted as 0%).

scholarly journals Cell-Fusing Agent Virus Reduces Arbovirus Dissemination in Aedes aegypti Mosquitoes In Vivo

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Artem Baidaliuk ◽  
Elliott F. Miot ◽  
Sebastian Lequime ◽  
Isabelle Moltini-Conclois ◽  
Fanny Delaigue ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Line ◽  
Content Type ◽  
Cells In Culture ◽  
Mosquito Cells ◽  
Wide Range ◽  
Natural Hosts

ABSTRACT Aedes aegypti mosquitoes are the main vectors of arthropod-borne viruses (arboviruses) of public health significance, such as the flaviviruses dengue virus (DENV) and Zika virus (ZIKV). Mosquitoes are also the natural hosts of a wide range of viruses that are insect specific, raising the question of their influence on arbovirus transmission in nature. Cell-fusing agent virus (CFAV) was the first described insect-specific flavivirus, initially discovered in an A. aegypti cell line and subsequently detected in natural A. aegypti populations. It was recently shown that DENV and the CFAV strain isolated from the A. aegypti cell line have mutually beneficial interactions in mosquito cells in culture. However, whether natural strains of CFAV and DENV interact in live mosquitoes is unknown. Using a wild-type CFAV isolate recently derived from Thai A. aegypti mosquitoes, we found that CFAV negatively interferes with both DENV type 1 and ZIKV in vitro and in vivo. For both arboviruses, prior infection by CFAV reduced the dissemination titer in mosquito head tissues. Our results indicate that the interactions observed between arboviruses and the CFAV strain derived from the cell line might not be a relevant model of the viral interference that we observed in vivo. Overall, our study supports the hypothesis that insect-specific flaviviruses may contribute to reduce the transmission of human-pathogenic flaviviruses. IMPORTANCE The mosquito Aedes aegypti carries several arthropod-borne viruses (arboviruses) that are pathogenic to humans, including dengue and Zika viruses. Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. Although interactions between cell-fusing agent virus and dengue virus have been documented in mosquito cells in culture, whether wild strains of cell-fusing agent virus interfere with arbovirus transmission by live mosquitoes was unknown. We used an experimental approach to demonstrate that cell-fusing agent virus infection reduces the propagation of dengue and Zika viruses in A. aegypti mosquitoes. These results support the idea that insect-only viruses in nature can modulate the ability of mosquitoes to carry arboviruses of medical significance and that they could possibly be manipulated to reduce arbovirus transmission.

scholarly journals Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

2004 ◽  
Vol 1 (2) ◽  
pp. 135-147 ◽  
Author(s):  
PHILIP R. LEE ◽  
JONATHAN E. COHEN ◽  
ELISABETTA A. TENDI ◽  
ROBERT FARRER ◽  
GEORGE H. DE VRIES ◽  
...  
Keyword(s):  
Cell Line ◽  
Schwann Cells ◽  
Western Blotting ◽  
Microarray Data ◽  
Cdna Microarrays ◽  
Type I ◽  
Nerve Sheath Tumor ◽  
Wide Range ◽  
Normal Human ◽  
Selection Of

cDNA microarrays were utilized to identify abnormally expressed genes in a malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by comparing the mRNA abundance profiles with that of normal human Schwann cells (nhSCs). The findings characterize the molecular phenotype of this important cell-line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs. In total, 4608 cDNA sequences were screened and hybridizations replicated on custom cDNA microarrays. In order to verify the microarray data, a large selection of differentially expressed mRNA transcripts were subjected to semi-quantitative reverse transcription PCR (LightCycler). Western blotting was performed to investigate a selection of genes and signal transduction pathways, as a further validation of the microarray data. The data generated from multiple microarray screens, semi-quantitative RT–PCR and Western blotting are in broad agreement. This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. This study has identified ∼900 genes that are expressed abnormally in the T265 cell line and detected many genes not previously reported to be expressed in nhSCs. The results provide crucial information on the T265 cells that is essential for investigation using this cell line in experimental studies in neurofibromatosis type I (NF1), and important information on normal human Schwann cells that is applicable to a wide range of studies on Schwann cells in cell culture.

scholarly journals In vivo selection of a highly metastatic cell line from a human pancreatic carcinoma in the nude mouse

Cancer ◽  
1992 ◽  
Vol 69 (8) ◽  
pp. 2060-2063 ◽  
Author(s):  
Michael P. Vezeridis ◽  
George N. Tzanakakis ◽  
Patricia A. Meitner ◽  
Craig M. Doremus ◽  
Lance M. Tibbetts ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Cell Line ◽  
Nude Mouse ◽  
In Vivo Selection ◽  
Metastatic Cell ◽  
Metastatic Cell Line ◽  
Selection Of

scholarly journals Organization on the plasma membrane of the retinitis pigmentosa protein RP2: investigation of association with detergent-resistant membranes and polarized sorting

2003 ◽  
Vol 372 (2) ◽  
pp. 427-433 ◽  
Author(s):  
J. Paul CHAPPLE ◽  
Celene GRAYSON ◽  
Alison J. HARDCASTLE ◽  
Tracey A. BAILEY ◽  
Karl MATTER ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Retinitis Pigmentosa ◽  
Cell Line ◽  
Lipid Rafts ◽  
Retinal Pigment ◽  
Significant Proportion ◽  
Wide Range ◽  
Detergent Resistant Membranes ◽  
Acylated Proteins

Mutations in the retinitis pigmentosa protein gene RP2 account for up to 15% of X-linked retinitis pigmentosa. RP2 is a novel protein of unknown function, which is targeted to the plasma membrane by dual N-terminal acyl-modification. Dual-acylated proteins are targeted to lipid rafts, and some are subject to polarized sorting. Therefore we investigated the organization of RP2 on the plasma membrane. Endogenous RP2 protein was predominantly localized at the plasma membrane, and exogenously expressed green-fluorescent-protein-tagged protein was also targeted to the membrane in a wide range of cultured cells. High levels of endogenous RP2 protein were present in HeLa cells and in the retinal pigment epithelium-derived cell line ARPE19. A significant proportion of RP2 in cultured neuroblastoma cells was associated with detergent-resistant membranes (DRMs), but much less than other dually acylated proteins (e.g. Lyn and Fyn). In contrast, the RP2-interacting protein Arl3 (ADP-ribosylation factor-like 3) was not found to be associated with DRMs. The association of RP2 with DRMs was cholesterol-dependent. In polarized epithelial cells in culture and in vivo, RP2 was present in both the apical and basolateral domains of the plasma membrane. These data show that RP2 is not specific to either domain, unlike some other dually acylated proteins. Interestingly, the level of RP2 protein increased in the epithelial cell line Caco-2 with differentiation and polarization. These data show that RP2 is present on the membrane of all cell types examined both in vitro and in vivo, and that RP2 associates with lipid rafts, suggesting a potential role for the protein in signal transduction.

The Analysis of Malignancy by Cell Fusion

1974 ◽  
Vol 16 (1) ◽  
pp. 189-198
Author(s):  
F. WIENER ◽  
G. KLEIN ◽  
H. HARRIS
Keyword(s):  
Cell Fusion ◽  
Tumour Cells ◽  
Complementation Analysis ◽  
Malignant Cells ◽  
Hybrid Cells ◽  
Malignant Phenotype ◽  
Recessive Character ◽  
Parental Chromosome ◽  
Wide Range

Previous studies with a variety of transplantable mouse tumours showed that in hybrids between malignant and non-malignant cells, malignancy behaved as a recessive character: the hybrid cells, so long as they retained something close to the complete parental chromosome sets, had little or no ability to grow progressively in vivo. In the experiments we now describe the heritable lesions determining the malignant phenotype were further explored by complementation analysis in which the various tumour cells were fused with each other. Forty-two clonal populations derived from twelve crosses between different kinds of tumour cells were examined. Only one cross generated hybrid cells with reduced tumorigenicity: in all other cases the hybrid cells formed were highly malignant. It thus appears that, in a wide range of different tumours, the lesions determining the malignant phenotype, although recessive, fail to complement each other.

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