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.

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

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.

The Analysis of Malignancy by Cell Fusion

1971 ◽  
Vol 8 (3) ◽  
pp. 681-692
Author(s):  
F. WIENER ◽  
G. KLEIN ◽  
H. HARRIS
Keyword(s):  
Tumour Cells ◽  
Hybrid Cells ◽  
Recessive Character ◽  
Parental Chromosome ◽  
Diploid Fibroblasts ◽  
Progressive Loss ◽  
L Cell ◽  
Very High

Diploid fibroblasts were fused with cells of two highly malignant near euploid tumours, a sarcoma induced by polyoma virus and a spontaneous carcinoma; the resulting hybrid cells were tested for their ability to grow progressively in vivo. In the case of the sarcoma/fibroblast hybrids, 15 clonal populations, each derived from a separate primary fusion, were examined. Most of these populations already showed substantial losses of chromosomes by the time enough cells had been generated to permit chromosomal analysis; but a few clones were isolated with chromosomal constitutions approximating to the sum of the 2 parental chromosome sets. Those clones that had undergone substantial chromosomal losses were highly tumorigenic, but some of the clones that contained the complete, or almost complete, chromosome sets of both parent cells, showed a greatly reduced take incidence. Initially these clones produced very few tumours, but the take incidence rose as continued cultivation of the cells in vitro resulted in progressive loss of chromosomes. In the case of the carcinoma/fibroblast hybrids, clonal populations with very high chromosome numbers were selected for special study. These were also found to have a very low take incidence, comparable to that of the hybrids formed by the fusion of the tumour cells with L cell derivatives. None of the tumours produced by the injection of either the sarcoma/fibroblast or carcinoma/fibroblast hybrids were composed of cells containing chromosome complements corresponding to the sum of the 2 parental chromosome sets; all the tumours were formed by selective overgrowth of cells from which some chromosomes had been eliminated. These results indicate that the malignancy of the tumour cells can be suppressed by diploid fibroblasts as well as by the L cell derivatives, but that the rapid chromosome losses characteristic of hybrids between these tumour cells and diploid fibroblasts generate malignant segregants with much greater frequency. In the range of material examined in the present experiments malignancy thus behaves as if it were a recessive character.

The suppression of malignancy by terminal differentiation: evidence from hybrids between tumour cells and keratinocytes

1987 ◽  
Vol 87 (3) ◽  
pp. 383-388
Author(s):  
H. Harris ◽  
M.E. Bramwell
Keyword(s):  
Terminal Differentiation ◽  
Human Keratinocytes ◽  
Tumour Cells ◽  
Human Cells ◽  
Hybrid Cells ◽  
Progressive Growth ◽  
Cultivation In Vitro

When malignant human cells are crossed with diploid human keratinocytes, malignancy, as defined by progressive growth in vivo, is suppressed so long as the hybrid cells continue to produce involucrin, a protein that characterizes terminal differentiation in the keratinocyte. When, on continued cultivation in vitro, the cells lose the ability to produce involucrin, they reacquire the ability to grow progressively in the animal.

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 antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophila

2019 ◽  
Author(s):  
Jean-Philippe Parvy ◽  
Yachuan Yu ◽  
Anna Dostalova ◽  
Shu Kondo ◽  
Alina Kurjan ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumour Necrosis Factor ◽  
Tumour Cell ◽  
Tumour Necrosis ◽  
Tumour Progression ◽  
Tumour Cells ◽  
Tumour Regression ◽  
Necrosis Factor

AbstractAntimicrobial peptides (AMPs) are small cationic molecules best known as mediators of the innate defence against microbial infection. While in vitro and ex vivo evidence suggest AMPs’ capacity to kill cancer cells, in vivo demonstration of an anti-tumour role of endogenous AMPs is lacking. Using a Drosophila model of tumourigenesis, we demonstrate a role for the AMP Defensin in the control of tumour progression. Our results reveal that Tumour Necrosis Factor mediates exposure of phosphatidylserine (PS), which makes tumour cells selectively sensitive to the action of Defensin remotely secreted from tracheal and fat tissues. Defensin binds tumour cells in PS-enriched areas, provoking cell death and tumour regression. Altogether, our results provide the first in vivo demonstration for a role of an endogenous AMP as an anti-cancer agent, as well as a mechanism that explains tumour cell sensitivity to the action of AMPs.

scholarly journals Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?

Oncogenesis ◽  
2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Sini Karinen ◽  
Krista Juurikka ◽  
Roosa Hujanen ◽  
Wafa Wahbi ◽  
Elin Hadler-Olsen ◽  
...  
Keyword(s):  
Tumour Cell ◽  
Lymphatic Metastasis ◽  
Tumour Cells ◽  
Metastatic Tumour ◽  
Tumour Metastasis ◽  
And Function ◽  
Cell Dissemination ◽  
Tumour Cell Dissemination

AbstractLymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSCC patients. In this study, we present a potential novel mechanism of lymphatic metastasis in OSCC—lymphatic mimicry (LM), a process whereby tumour cells form cytokeratin+/LYVE-1+, but podoplanin-negative, mosaic endothelial-like vessels. LM was detected in one-third (20/57; 35.08%) of randomly selected OSCC patients. The LM-positive patients had shorter overall survival (OS) compared to LM-negative group albeit not statistically significant. Highly-metastatic tumour cells formed distinct LM structures in vitro and in vivo. Importantly, the siRNA-mediated knockdown of LYVE-1 not only impaired tumour cell migration but also blunted their capacity to form LM-vessels in vitro and reduced tumour metastasis in vivo. Together, our findings uncovered, to our knowledge, a previously unknown expression and function of LYVE-1 in OSCC, whereby tumour cells could induce LM formation and promote lymphatic metastasis. Finally, more detailed studies on LM are warranted to better define this phenomenon in the future. These studies could benefit the development of targeted therapeutics for blocking tumour-related lymphangiogenesis.

scholarly journals Suppression of malignancy in hybrid cells: the mechanism

1985 ◽  
Vol 79 (1) ◽  
pp. 83-94 ◽  
Author(s):  
H. Harris
Keyword(s):  
Extracellular Matrix ◽  
Terminal Differentiation ◽  
Parent Cell ◽  
Malignant Cells ◽  
Hybrid Cells ◽  
Malignant Phenotype ◽  
Diploid Parent ◽  
Wide Range ◽  
Secondary Consequence

When malignant cells, defined by their ability to grow progressively in genetically compatible hosts, are fused with diploid fibroblasts of the same species, the resulting hybrid cells, so long as they retain certain specific chromosomes donated by the diploid parent cell, are non-malignant. When these particular chromosomes are eliminated from the hybrid, the malignant phenotype reappears, and the segregant cell is again able to grow progressively in vivo. In the present experiments the histological character of the lesions produced by the inoculation of crosses between malignant and non-malignant cells was examined. It was found, in a wide range of material, and without exception, that where one or other of the parent cells in the cross was of fibroblastic lineage, malignancy was suppressed when the hybrid cells produced a collagenous extracellular matrix in vivo; and it reappeared when genetic segregants were produced that had lost the ability to produce this matrix. These results are interpreted in terms of a general model in which it is proposed that the progressive multiplication of malignant cells in vivo is a secondary consequence of a genetically stable impairment of terminal differentiation.

scholarly journals Inhibitory effect of yoghurt and soya yoghurt containing bifidobacteria on the proliferation of Ehrlich ascites tumour cells in vitro and in vivo in a mouse tumour model

2004 ◽  
Vol 92 (1) ◽  
pp. 81-86 ◽  
Author(s):  
I. A. Abd El-Gawad ◽  
E. M. El-Sayed ◽  
S. A. Hafez ◽  
H. M. El-Zeini ◽  
F. A. Saleh
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Tumour Cells ◽  
Soya Milk ◽  
Ascites Tumour ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour ◽  
Tumour Cell Proliferation

The effect of yoghurt and soya yoghurt containing Bifidobacterium lactis Bb-12 or B. longum Bb-46 on Ehrlich ascites tumour cell proliferation was investigated in vitro and in vivo. Tumour cells were incubated with B. lactis Bb-12 or B. longum Bb-46 cultivated in de Mann Rogosa Sharpe (MRS) broth medium, or with their centrifuged supernatant fractions or sediments, for 2 h at 37°C. Treatment resulted in the inhibition of tumour cell proliferation by 85·42 (sd 0·78) and 85·10 (sd 1·28) % by intact micro-organisms, 77·61 (sd 0·29) and 71·43 (sd 1·75) % by their supernatant fractions, but only 4·00 (sd 0·19) and 9·09 (sd 1·24) % by the two sedimented bacteria, respectively. The incubation of tumour cells with yoghurt and soya yoghurt containing Bb-12 for 2 h resulted in 83·01 (sd 0·11) and 88·23 (sd 0·06) % inhibition, respectively, while it was 83·82 (sd 0·24) and 86·36 (sd 0·06) %, respectively for the same products containing Bb-46. Corresponding values for plain yoghurt and soya milk (without bifidobacteria) were 32·81 (sd 0·14) and 5·55 (sd 0·12) %, respectively. The differences between yoghurt or soya yoghurt containing Bb-12 or Bb-46 and plain yoghurt, soya milk or control treatments were statistically significant (n 3; P>0·05). Female Swiss albino mice were injected intraperitoneally with the same tumour cells. The lifespan of mice fed diets supplemented with yoghurt or soya yoghurt containing Bb-12 or Bb-46 was prolonged by 16, 23, 34 and 39%, respectively compared with that of the positive control group (n 6; P>0·05). The lifespan of groups fed plain yoghurt or soya milk was prolonged by 15 and 8%, respectively. Prolongation of lifespan was positively correlated with faeces bifidobacterial count in the groups fed yoghurt or soya yoghurt containing bifidobacteria (r 0·917; P>0·05).

scholarly journals Epigenetics changes caused by the fusion of human embryonic stem cell and ovarian cancer cells

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Ke He ◽  
Hu Qu ◽  
Li-Nan Xu ◽  
Jun Gao ◽  
Fu-Yi Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Tumour Cells ◽  
Ovarian Cancer Cells ◽  
Hybrid Cells

To observe the effect of gene expression and tumorigenicity in hybrid cells of human embryonic stem cells (hESCs) and ovarian cancer cells in vitro and in vivo using a mouse model, and to determine its feasibility in reprogramming tumour cells growth and apoptosis, for a potential exploration of the role of hESCs and tumour cells fusion in the management of ovarian cancer. Stable transgenic hESCs (H1) and ovarian cancer cell line OVCAR-3 were established before fusion, and cell fusion system was established to analyse the related indicators. PTEN expression in HO-H1 cells was higher than those in the parental stem cells and lower than those in parental tumour cells; the growth of OV-H1 (RFP+GFP) hybrid cells with double fluorescence expressions were obviously slower than that of human embryonic stem cells and OVCAR-3 ovarian cancer cells. The apoptosis signal of the OV-H1 hybrid cells was significantly higher than that of the hESCs and OVCAR-3 ovarian cancer cells. In vivo results showed that compared with 7 days, 28 days and 35 days after inoculation of OV-H1 hybrid cells; also, apoptotic cell detection indicated that much stronger apoptotic signal was found in OV-H1 hybrid cells inoculated mouse. The hESCs can inhibit the growth of OVCAR-3 cells in vitro by suppressing p53 and PTEN expression to suppress the growth of tumour that may be achieved by inducing apoptosis of OVCAR-3 cells. The change of epigenetics after fusion of ovarian cancer cells and hESCs may become a novel direction for treatment of ovarian cancer.

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