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Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells

Institute of Immunology & Experimental Oncology, Center for Biomedical Education and Research (ZBAF), University of Witten/Herdecke, Witten 58453, Germany
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Academic Editor: Wilhelm Bloch
Int. J. Mol. Sci. 2015, 16(12), 30362-30381; https://doi.org/10.3390/ijms161226240
Received: 4 November 2015 / Revised: 7 December 2015 / Accepted: 9 December 2015 / Published: 19 December 2015
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)
The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could originate in (human) cancers and could contribute to the progression of the disease is still missing, suggesting that the cell fusion hypothesis is rather fiction than fact. However, is the lack of this ultimate proof a valid argument against this hypothesis, particularly if one has to consider that appropriate markers do not (yet) exist, thus making it virtually impossible to identify a human tumor cell clearly as a tumor hybrid cell. In the present review, we will summarize the evidence supporting the cell fusion in cancer concept. Moreover, we will refine the cell fusion hypothesis by providing evidence that cell fusion is a potent inducer of aneuploidy, genomic instability and, most likely, even chromothripsis, suggesting that cell fusion, like mutations and aneuploidy, might be an inducer of a mutator phenotype. Finally, we will show that “accidental” tissue repair processes during cancer therapy could lead to the origin of therapy resistant cancer hybrid stem cells. View Full-Text
Keywords: cell fusion; tissue regeneration; cancer; mutator phenotype; mutations; aneuploidy; genomic instability; chromothripsis cell fusion; tissue regeneration; cancer; mutator phenotype; mutations; aneuploidy; genomic instability; chromothripsis
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Dittmar, T.; Zänker, K.S. Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells. Int. J. Mol. Sci. 2015, 16, 30362-30381.

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