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A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

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Cell fusion as a link between viruses and carcinogenesis. Potential implications of our findings to carcinogenesis could be summarized by the following speculative model. Although illicit cell fusion induced by viruses may be a frequent and common event, it usually has no consequences for carcinogenesis because, as a rule, the resulting cells either die or do not proliferate. However, if the cells have a deregulated cell cycle and if the virus tends to produce dikaryons rather than syncytia, the fused cells may proliferate. The majority of these cells, however, die within a few cell divisions because of chromosomal aberrations associated with abnormal mitoses or other, yet unrecognized, consequences of cell fusion. However, the few cells that survive are abnormal in that they have a deregulated cell cycle, lack normal response to this deregulation, are aneuploid, and have epigenetic regulation that is an unpredictable result of the merger between fusion partners. A combination of these properties in a minute fraction of the fused cells may be sufficient to make them cancerous. Considering that a single cell can give rise to a cancer, the frequency with which cell fusion produces such cells does not need to be high to have pathological consequences.
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fig9: Cell fusion as a link between viruses and carcinogenesis. Potential implications of our findings to carcinogenesis could be summarized by the following speculative model. Although illicit cell fusion induced by viruses may be a frequent and common event, it usually has no consequences for carcinogenesis because, as a rule, the resulting cells either die or do not proliferate. However, if the cells have a deregulated cell cycle and if the virus tends to produce dikaryons rather than syncytia, the fused cells may proliferate. The majority of these cells, however, die within a few cell divisions because of chromosomal aberrations associated with abnormal mitoses or other, yet unrecognized, consequences of cell fusion. However, the few cells that survive are abnormal in that they have a deregulated cell cycle, lack normal response to this deregulation, are aneuploid, and have epigenetic regulation that is an unpredictable result of the merger between fusion partners. A combination of these properties in a minute fraction of the fused cells may be sufficient to make them cancerous. Considering that a single cell can give rise to a cancer, the frequency with which cell fusion produces such cells does not need to be high to have pathological consequences.

Mentions: However, Koch's postulates are valid only if the causal relationship between viruses and oncogenic transformation is as direct as that between viruses and infectious diseases, which is an assumption that is consistent with the current view of viral oncogenesis. If the causal relationship between viruses and oncogenic transformation includes events with random outcomes in respect to carcinogenesis, such as cell fusion and abnormal mitoses, and the virus may even be absent in the cells it produced, then the cause–effect relationship between viruses and cancer is intrinsically stochastic (Fig. 9), which would mean that Koch's postulates do not apply. Therefore, the observed correlations between viral infections and human cancer may be more than coincidental, even though because of its random nature it may be impossible, in principle, to establish a mechanistic link by analyzing only cancer cells.


A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Cell fusion as a link between viruses and carcinogenesis. Potential implications of our findings to carcinogenesis could be summarized by the following speculative model. Although illicit cell fusion induced by viruses may be a frequent and common event, it usually has no consequences for carcinogenesis because, as a rule, the resulting cells either die or do not proliferate. However, if the cells have a deregulated cell cycle and if the virus tends to produce dikaryons rather than syncytia, the fused cells may proliferate. The majority of these cells, however, die within a few cell divisions because of chromosomal aberrations associated with abnormal mitoses or other, yet unrecognized, consequences of cell fusion. However, the few cells that survive are abnormal in that they have a deregulated cell cycle, lack normal response to this deregulation, are aneuploid, and have epigenetic regulation that is an unpredictable result of the merger between fusion partners. A combination of these properties in a minute fraction of the fused cells may be sufficient to make them cancerous. Considering that a single cell can give rise to a cancer, the frequency with which cell fusion produces such cells does not need to be high to have pathological consequences.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171256&req=5

fig9: Cell fusion as a link between viruses and carcinogenesis. Potential implications of our findings to carcinogenesis could be summarized by the following speculative model. Although illicit cell fusion induced by viruses may be a frequent and common event, it usually has no consequences for carcinogenesis because, as a rule, the resulting cells either die or do not proliferate. However, if the cells have a deregulated cell cycle and if the virus tends to produce dikaryons rather than syncytia, the fused cells may proliferate. The majority of these cells, however, die within a few cell divisions because of chromosomal aberrations associated with abnormal mitoses or other, yet unrecognized, consequences of cell fusion. However, the few cells that survive are abnormal in that they have a deregulated cell cycle, lack normal response to this deregulation, are aneuploid, and have epigenetic regulation that is an unpredictable result of the merger between fusion partners. A combination of these properties in a minute fraction of the fused cells may be sufficient to make them cancerous. Considering that a single cell can give rise to a cancer, the frequency with which cell fusion produces such cells does not need to be high to have pathological consequences.
Mentions: However, Koch's postulates are valid only if the causal relationship between viruses and oncogenic transformation is as direct as that between viruses and infectious diseases, which is an assumption that is consistent with the current view of viral oncogenesis. If the causal relationship between viruses and oncogenic transformation includes events with random outcomes in respect to carcinogenesis, such as cell fusion and abnormal mitoses, and the virus may even be absent in the cells it produced, then the cause–effect relationship between viruses and cancer is intrinsically stochastic (Fig. 9), which would mean that Koch's postulates do not apply. Therefore, the observed correlations between viral infections and human cancer may be more than coincidental, even though because of its random nature it may be impossible, in principle, to establish a mechanistic link by analyzing only cancer cells.

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

Show MeSH
Related in: MedlinePlus