scholarly journals Cell–Cell Fusion and the Roads to Novel Properties of Tumor Hybrid Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1465
Author(s):  
Mareike Sieler ◽  
Julian Weiler ◽  
Thomas Dittmar
Keyword(s):  
Cell Fusion ◽  
Small Population ◽  
Epigenetic Alterations ◽  
Hybrid Cells ◽  
Daughter Cells ◽  
Whole Process ◽  
Random Segregation ◽  
Metastatic Capacity ◽  
Unique Manner ◽  
Cell Cell

The phenomenon of cancer cell–cell fusion is commonly associated with the origin of more malignant tumor cells exhibiting novel properties, such as increased drug resistance or an enhanced metastatic capacity. However, the whole process of cell–cell fusion is still not well understood and seems to be rather inefficient since only a certain number of (cancer) cells are capable of fusing and only a rather small population of fused tumor hybrids will survive at all. The low survivability of tumor hybrids is attributed to post-fusion processes, which are characterized by the random segregation of mixed parental chromosomes, the induction of aneuploidy and further random chromosomal aberrations and genetic/epigenetic alterations in daughter cells. As post-fusion processes also run in a unique manner in surviving tumor hybrids, the occurrence of novel properties could thus also be a random event, whereby it might be speculated that the tumor microenvironment and its spatial habitats could direct evolving tumor hybrids towards a specific phenotype.

scholarly journals Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy

2020 ◽  
Vol 21 (5) ◽  
pp. 1811 ◽  
Author(s):  
Jessica Dörnen ◽  
Mareike Sieler ◽  
Julian Weiler ◽  
Silvia Keil ◽  
Thomas Dittmar
Keyword(s):  
Genomic Instability ◽  
Cell Fusion ◽  
Tissue Regeneration ◽  
Hybrid Cells ◽  
Daughter Cells ◽  
Physiological Processes ◽  
Multipolar Spindles ◽  
First Results ◽  
Random Segregation ◽  
A Cell

The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.

scholarly journals Cell–cell fusion of mesenchymal cells with distinct differentiations triggers genomic and transcriptomic remodelling toward tumour aggressiveness

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lucile Delespaul ◽  
Caroline Gélabert ◽  
Tom Lesluyes ◽  
Sophie Le Guellec ◽  
Gaëlle Pérot ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Cell Fusion ◽  
Mesenchymal Cells ◽  
Tumour Cells ◽  
Physiological Process ◽  
Hybrid Cells ◽  
Transcriptomic Profile ◽  
Transformed Fibroblasts ◽  
Histological Characteristics ◽  
Cell Cell

AbstractCell–cell fusion is a physiological process that is hijacked during oncogenesis and promotes tumour evolution. The main known impact of cell fusion is to promote the formation of metastatic hybrid cells following fusion between mobile leucocytes and proliferating tumour cells. We show here that cell fusion between immortalized myoblasts and transformed fibroblasts, through genomic instability and expression of a specific transcriptomic profile, leads to emergence of hybrid cells acquiring dissemination properties. This is associated with acquisition of clonogenic ability by fused cells. In addition, by inheriting parental properties, hybrid tumours were found to mimic the histological characteristics of a specific histotype of sarcomas: undifferentiated pleomorphic sarcomas with incomplete muscular differentiation. This finding suggests that cell fusion, as macroevolution event, favours specific sarcoma development according to the differentiation lineage of parent cells.

scholarly journals Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell–cell fusion

2012 ◽  
Vol 197 (4) ◽  
pp. 553-568 ◽  
Author(s):  
Tsukasa Oikawa ◽  
Masaaki Oyama ◽  
Hiroko Kozuka-Hata ◽  
Shunsuke Uehara ◽  
Nobuyuki Udagawa ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Differentiation ◽  
Cell Fusion ◽  
Underlying Mechanism ◽  
Hybrid Cells ◽  
Multinucleated Cells ◽  
Phosphoinositide 3 Kinase ◽  
Inflammatory Milieu ◽  
Invadopodia Formation ◽  
Cell Cell

Osteoclasts fuse to form multinucleated cells during osteoclastogenesis. This process is mediated by dynamic rearrangement of the plasma membrane and cytoskeleton, and it requires numerous factors, many of which have been identified. The underlying mechanism remains obscure, however. In this paper, we show that Tks5, a master regulator of invadopodia in cancer cells, is crucial for osteoclast fusion downstream of phosphoinositide 3-kinase and Src. Expression of Tks5 was induced during osteoclastogenesis, and prevention of this induction impaired both the formation of circumferential podosomes and osteoclast fusion without affecting cell differentiation. Tyrosine phosphorylation of Tks5 was attenuated in Src−/− osteoclasts, likely accounting for defects in podosome organization and multinucleation in these cells. Circumferential invadopodia formation in B16F0 melanoma cells was also accompanied by Tks5 phosphorylation. Co-culture of B16F0 cells with osteoclasts in an inflammatory milieu promoted the formation of melanoma–osteoclast hybrid cells. Our results thus reveal an unexpected link between circumferential podosome/invadopodium formation and cell–cell fusion in and beyond osteoclasts.

scholarly journals Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6130 ◽  
Author(s):  
Yoshiyuki Yamada ◽  
Xiao Bo Liu ◽  
Shou Guo Fang ◽  
Felicia P. L. Tay ◽  
Ding Xiang Liu
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Cultured Cells ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
Fusion Activity ◽  
Cell Cell

scholarly journals Elizabeth Chen: Fusing cells press closer

2014 ◽  
Vol 206 (5) ◽  
pp. 576-577
Author(s):  
Caitlin Sedwick
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Chen studies cell–cell fusion in Drosophila myoblasts.

scholarly journals A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins

2008 ◽  
Vol 4 (3) ◽  
pp. e1000016 ◽  
Author(s):  
Jayme Salsman ◽  
Deniz Top ◽  
Christopher Barry ◽  
Roy Duncan
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Methodologies in the Study of Cell–Cell Fusion

Methods ◽  
1998 ◽  
Vol 16 (2) ◽  
pp. 215-226 ◽  
Author(s):  
Fredric S. Cohen ◽  
Grigory B. Melikyan
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

2021 ◽  
Vol 46 (1) ◽  
Author(s):  
Xiao-Chun Peng ◽  
Min Zhang ◽  
Ying-Ying Meng ◽  
Yan-Fang Liang ◽  
Ying-Ying Wang ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Tumor Metastasis ◽  
Cell Cell

Herpes simplex virus glycoprotein B (gB) mutations define structural sites in domain I, the membrane proximal region, and the cytodomain that regulate entry.

2021 ◽  
Author(s):  
Qing Fan ◽  
Richard Longnecker ◽  
Sarah A. Connolly
Keyword(s):  
Cell Fusion ◽  
Virus Entry ◽  
Proximal Region ◽  
Glycoprotein B ◽  
Viral Fusion ◽  
Viral Fusion Protein ◽  
Membrane Proximal Region ◽  
Domain V ◽  
Domain I ◽  
Cell Cell

The viral fusion protein glycoprotein B (gB) is conserved in all herpesviruses and is essential for virus entry. During entry, gB fuses viral and host cell membranes by refolding from a prefusion to a postfusion form. We previously introduced three structure-based mutations (gB-I671A/H681A/F683A) into the domain V arm of the gB ectodomain that resulted in reduced cell-cell fusion. A virus carrying these three mutations (called gB3A) displayed a small plaque phenotype and remarkably delayed entry into cells. To identify mutations that could counteract this phenotype, we serially passaged the gB3A virus and selected for revertant viruses with increased plaque size. Genomic sequencing revealed that the revertant viruses had second-site mutations in gB, including E187A, M742T, and S383F/G645R/V705I/V880G. Using expression constructs encoding these mutations, only gB-V880G was shown to enhance cell-cell fusion. In contrast, all of the revertant viruses showed enhanced entry kinetics, underscoring the fact that cell-cell fusion and virus-cell fusion are different. The results indicate that mutations in three different regions of gB (domain I, the membrane proximal region, and the cytoplasmic tail domain) can counteract the slow entry phenotype of gB3A virus. Mapping these compensatory mutations to prefusion and postfusion structural models suggests sites of intramolecular functional interactions with the gB domain V arm that may contribute to the gB fusion function. Importance The nine human herpesviruses are ubiquitous and cause a range of disease in humans. Glycoprotein B (gB) is an essential viral fusion protein that is conserved in all herpesviruses. During host cell entry, gB mediates virus-cell membrane fusion by undergoing a conformational change. Structural models for the prefusion and postfusion form of gB exist, but the details of how the protein converts from one to the other are unclear. We previously introduced structure-based mutations into gB that inhibited virus entry and fusion. By passaging this entry-deficient virus over time, we selected second-site mutations that partially restore virus entry. The location of these mutations suggest regulatory sites that contribute to fusion and gB refolding during entry. gB is a target of neutralizing antibodies and defining how gB refolds during entry could provide a basis for the development of fusion inhibitors for future research or clinical use.

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