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.

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.

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 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. 673-680
Author(s):  
U. BREGULA ◽  
G. KLEIN ◽  
H. HARRIS
Keyword(s):  
Cell Fusion ◽  
Chromosomal Analysis ◽  
Cell Populations ◽  
Hybrid Cells ◽  
Parental Chromosome ◽  
Chromosomal Constitution ◽  
Diploid Fibroblasts ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells

When Ehrlich ascites cells were fused with diploid fibroblasts, isolated directly from the animal, the resulting hybrid cells regularly produced progressive tumours. However, an analysis of a range of clonal populations of these hybrid cells, each derived from a separate primary fusion, revealed that the chromosomal constitution of these cells was highly unstable; all cell populations were found to have already undergone substantial chromosome losses by the time enough cells were available to permit chromosomal analysis. Thus, although these hybrid cells were highly tumorigenic, the tumours arising from them were not composed of cells with complete parental chromosome sets, but of cells from which some chromosomes had been eliminated.

scholarly journals Hybrid Formation and Fusion of Cancer Cells In Vitro and In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4496
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Thomas Dittmar
Keyword(s):  
Cell Fusion ◽  
Cancer Cell ◽  
Selection Process ◽  
Hybrid Cell ◽  
Chromosomal Rearrangements ◽  
Immune Surveillance ◽  
Hybrid Cells ◽  
Tumor Plasticity

The generation of cancer hybrid cells by intra-tumoral cell fusion opens new avenues for tumor plasticity to develop cancer stem cells with altered properties, to escape from immune surveillance, to change metastatic behavior, and to broaden drug responsiveness/resistance. Genomic instability and chromosomal rearrangements in bi- or multinucleated aneuploid cancer hybrid cells contribute to these new functions. However, the significance of cell fusion in tumorigenesis is controversial with respect to the low frequency of cancer cell fusion events and a clonal advantage of surviving cancer hybrid cells following a post-hybrid selection process. This review highlights alternative processes of cancer hybrid cell development such as entosis, emperipolesis, cannibalism, therapy-induced polyploidization/endoreduplication, horizontal or lateral gene transfer, and focusses on the predominant mechanisms of cell fusion. Based upon new properties of cancer hybrid cells the arising clinical consequences of the subsequent tumor heterogeneity after cancer cell fusion represent a major therapeutic challenge.

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.

Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor

1983 ◽  
Vol 3 (4) ◽  
pp. 523-538
Author(s):  
R S Kerbel ◽  
A E Lagarde ◽  
J W Dennis ◽  
T P Donaghue
Keyword(s):  
Bone Marrow ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cell Fusion ◽  
Chromosome Segregation ◽  
Host Cells ◽  
Recessive Character ◽  
Ploidy Levels ◽  
Normal Host

Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGAr) mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAs) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4 (WGAr) tumor cells and normal host cells, at least some of which are of bone marrow origin. Thus, growth of the H-2d MDW4 tumor cells in (C3H X DBA/2)F1 (H-2k X H-2d) or (C57BL/6 X DBA/2)F1 (H-2b X H-2d) mice led to the appearance of WGAs revertants bearing the H-2k or H-2b major histocompatibility complex antigens associated with the C3H or C57BL/6 parental strains, respectively. Similarly, WGAs revertants of MDW4 were found to express H-2k antigens after growth in CBA/HT6T6 (H-2k) leads to DBA/2 bone marrow radiation chimeras. Attempts to mimic the in vivo hybridization process were successful in that in vitro somatic cell fusion between an ouabain-resistant (OuaR), 6-thioguanine-resistant (Thgr) derivative of the MDW4 mutant and either normal bone marrow or spleen cells resulted in loss of the WGAr phenotype in the hybrids (thus showing its recessive character) and increased malignant properties in vivo. An analysis of spontaneous frequencies of re-expression of various drug resistance genetic markers in several hybrid metastatic cells was also consistent with chromosome segregation of the sensitive alleles. The results show that tumor progression and the emergence of metastatic cell variants could arise as a consequence of tumor X host cell fusion followed by chromosome segregation. We also discuss the possibility that this type of event may normally be a very rare one during the growth of tumors, the frequency of which can be artificially amplified by the use of certain classes of lectin-resistant mutants carrying particular cell surface alterations.

scholarly journals Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor.

1983 ◽  
Vol 3 (4) ◽  
pp. 523-538 ◽  
Author(s):  
R S Kerbel ◽  
A E Lagarde ◽  
J W Dennis ◽  
T P Donaghue
Keyword(s):  
Bone Marrow ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cell Fusion ◽  
Chromosome Segregation ◽  
Host Cells ◽  
Recessive Character ◽  
Ploidy Levels ◽  
Normal Host

Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGAr) mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAs) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4 (WGAr) tumor cells and normal host cells, at least some of which are of bone marrow origin. Thus, growth of the H-2d MDW4 tumor cells in (C3H X DBA/2)F1 (H-2k X H-2d) or (C57BL/6 X DBA/2)F1 (H-2b X H-2d) mice led to the appearance of WGAs revertants bearing the H-2k or H-2b major histocompatibility complex antigens associated with the C3H or C57BL/6 parental strains, respectively. Similarly, WGAs revertants of MDW4 were found to express H-2k antigens after growth in CBA/HT6T6 (H-2k) leads to DBA/2 bone marrow radiation chimeras. Attempts to mimic the in vivo hybridization process were successful in that in vitro somatic cell fusion between an ouabain-resistant (OuaR), 6-thioguanine-resistant (Thgr) derivative of the MDW4 mutant and either normal bone marrow or spleen cells resulted in loss of the WGAr phenotype in the hybrids (thus showing its recessive character) and increased malignant properties in vivo. An analysis of spontaneous frequencies of re-expression of various drug resistance genetic markers in several hybrid metastatic cells was also consistent with chromosome segregation of the sensitive alleles. The results show that tumor progression and the emergence of metastatic cell variants could arise as a consequence of tumor X host cell fusion followed by chromosome segregation. We also discuss the possibility that this type of event may normally be a very rare one during the growth of tumors, the frequency of which can be artificially amplified by the use of certain classes of lectin-resistant mutants carrying particular cell surface alterations.

scholarly journals Asymmetric chromatin capture and nuclear envelopes separate endogenous and ectopic chromosomes after induced cell fusion

2020 ◽  
Author(s):  
Bharath Sunchu ◽  
Nicole Lee ◽  
Roberto Carlos Segura ◽  
Clemens Cabernard
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fusion ◽  
Metaphase Plate ◽  
Tumor Formation ◽  
Separation Mechanism ◽  
Dependent Manner ◽  
Hybrid Cells ◽  
Mother Cells

Metazoan cells accurately attach to, congress and segregate chromosomes during mitosis Additionally, hybrid cells derived through fertilization or somatic cell fusion also employ mechanisms to recognize and separate chromosomes of different origin. The underlying mechanisms are mostly unknown but could prevent aneuploidy and tumor formation. Here, we acutely induce fusion betweenDrosophilaneural stem cells (neuroblasts) and differentiating ganglion mother cells (GMCs)in vivoto define how epigenetically distinct chromatin is recognized and segregated. We find that Nb-GMC hybrid cells align both endogenous (neuroblast-origin) and ectopic (GMC-origin) chromosomes at the metaphase plate through centrosome derived dual spindles. Mixing of endogenous and ectopic chromatin is prevented through an asymmetric, microtubule-dependent chromatin capture mechanism during interphase and physical boundaries imposed by nuclear envelopes. Although hybrid cells fail to accurately segregate ectopic chromatin, manifested in lagging chromosomes and chromosome bridges, transplanted brain tissue containing hybrid cells neither reduce the lifespan nor form visible tumors in host flies. We conclude that fly neural stem cells utilize asymmetric centrosome activity in interphase to capture and physically separate epigenetically distinct chromatin in a microtubule-dependent manner. We propose a novel chromosome recognition and separation mechanism that could also inform biased chromatid segregation observed in flies and vertebrates.

Studies on the surface properties of hybrid cells. III. A membrane glycoprotein found on the surface of a wide range of malignant cells

1981 ◽  
Vol 48 (1) ◽  
pp. 147-170
Author(s):  
M.A. Atkinson ◽  
M.E. Bramwell
Keyword(s):  
Sialic Acid ◽  
Molecular Mass ◽  
Surface Properties ◽  
Apparent Molecular Mass ◽  
Membrane Glycoprotein ◽  
Malignant Cells ◽  
Hybrid Cells ◽  
Wide Range

We report here the presence of a glycoprotein of apparent molecular mass 90000 daltons on the surface of membranes of malignant cells, which is absent or very much reduced on the surface of non-malignant cells. This glycoprotein is rich in sialic acid and appears to be sensitive to the concentration of cAMP under certain conditions. Analysis of the labelled sugars present in the glycoproteins of cells metabolically labelled with [14C]glucosamine suggests that all the enzymes necessary for the conversion of the tracer precursor into the sugars normally found to be labelled are present in both the malignant and the non-malignant cells.

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