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

Hass, Ralf; Ohe, Juliane von der; Dittmar, Thomas

doi:10.3390/cancers13174496

Cited by 25 publications

(23 citation statements)

References 213 publications

(400 reference statements)

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“…In addition to its putative role in carcinogenesis cell-cell fusion has been further associated with tumor progression. Indeed, a plethora of studies demonstrated that homotypic (tumor cell × tumor cell) and heterotypic (tumor cell × normal cell) fusion events could give rise to hybrids exhibiting an increased metastatic capacity, an enhanced drug resistance, or even cancer stem/initiating cell properties (for review see: [99,[166][167][168][169][170][171][172]). In any case, despite the increasing knowledge about the impact of cell-cell fusion in tumor progression only a few proteins/phospholipids and conditions have been identified so far, which trigger the hybridization of cancer cells.…”

Section: Induction Of Cell-cell Fusion By Virus-derived Fusogens and Putative Correlation To Tumorsmentioning

confidence: 99%

“…Albeit syncytin-1 was reported to improve the prognosis of breast cancer patients [65], most data from other carcinoma types rather indicated a relationship between syncyctin-1 and tumor progression [59,61,64,66]. These findings also suggested that fusion of cancer cells in general develops a more malignant phenotype with progression of metastatic lesions [16,20,22,99,167,169,170,172]. Further involvement of syncytin-1 in the fusion of two non-transformed cells undergoing a malignant conversion has not yet been reported and, hence, remains ambiguous.…”

Section: Syncytin-1mentioning

confidence: 99%

“…Cell-cell fusion has been suggested as a putative driver of tumor initiation and progression [20,99,167,168,172,232,233]. However, despite increasing knowledge the entire mechanism is still scarcely understood.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Dittmar

Weiler

Luo

et al. 2021

Cancers

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Cell fusion is a well-known, but still scarcely understood biological phenomenon, which might play a role in cancer initiation, progression and formation of metastases. Although the merging of two (cancer) cells appears simple, the entire process is highly complex, energy-dependent and tightly regulated. Among cell fusion-inducing and -regulating factors, so-called fusogens have been identified as a specific type of proteins that are indispensable for overcoming fusion-associated energetic barriers and final merging of plasma membranes. About 8% of the human genome is of retroviral origin and some well-known fusogens, such as syncytin-1, are expressed by human (cancer) cells. Likewise, enveloped viruses can enable and facilitate cell fusion due to evolutionarily optimized fusogens, and are also capable to induce bi- and multinucleation underlining their fusion capacity. Moreover, multinucleated giant cancer cells have been found in tumors derived from oncogenic viruses. Accordingly, a potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion will be summarized in this review.

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Section: Induction Of Cell-cell Fusion By Virus-derived Fusogens and Putative Correlation To Tumorsmentioning

confidence: 99%

Section: Syncytin-1mentioning

confidence: 99%

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Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Dittmar

Weiler

Luo

et al. 2021

Cancers

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“…Alternative mechanisms that resemble cancer-cell fusion are mediated by cell cannibalism, entosis, and emperipolesis that form so-called cell-in-cell structures with the exchange of DNA [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Moreover, genes and mRNAs of fusion markers could be transferred by horizontal/lateral gene transfer or via extracellular vesicles, thereby altering the phenotype of recipient cells [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Hass

Ohe

Dittmar

2021

Cancers

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Fusion of cancer cells either with other cancer cells (homotypic fusion) in local vicinity of the tumor tissue or with other cell types (e.g., macrophages, cancer-associated fibroblasts (CAFs), mesenchymal stromal-/stem-like cells (MSC)) (heterotypic fusion) represents a rare event. Accordingly, the clinical relevance of cancer-cell fusion events appears questionable. However, enhanced tumor growth and/or development of certain metastases can originate from cancer-cell fusion. Formation of hybrid cells after cancer-cell fusion requires a post-hybrid selection process (PHSP) to cope with genomic instability of the parental nuclei and reorganize survival and metabolic functionality. The present review dissects mechanisms that contribute to a PHSP and resulting functional alterations of the cancer hybrids. 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. However, cellular partners during cancer-cell fusion such as MSC within the tumor microenvironment or MSC-derived exosomes may provide a suitable vehicle to specifically address and deliver anti-tumor cargo to cancer cells.

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“…This is due to post-fusion processes that are accompanied by improper segregation of chromosomes, impaired proliferation, or cell death ( Sieler et al, 2021 ). After fusion, some THCs remain multinucleated, others undergo a transition “from heterokaryon to syncarion” or a decrease in ploidy ( Hass et al, 2021 ). Although most THCs usually become more aggressive than the parental cells, cancer cell aggressiveness may also decrease after fusion ( Staroselsky et al, 1991 ).…”

Section: Tumor Hybrid Cells Formation: Factors and Mechanismsmentioning

confidence: 99%

Tumor Hybrid Cells: Nature and Biological Significance

Tretyakova

Subbalakshmi

Menyailo

et al. 2022

Front. Cell Dev. Biol.

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Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate, and avoiding immune surveillance. Experimental studies showed the association of THCs with a high frequency of cancer metastasis; however, the underlying mechanisms remain unclear. Many other questions also remain to be answered: the role of genetic alterations in tumor cell fusion, the molecular landscape of cells after fusion, the lifetime and fate of different THCs, and the specific markers of THCs, and their correlation with various cancers and clinicopathological parameters. In this review, we discuss the factors and potential mechanisms involved in the occurrence of THCs, the types of THCs, and their role in cancer drug resistance and metastasis, as well as potential therapeutic approaches for the prevention, and targeting of tumor cell fusion. In conclusion, we emphasize the current knowledge gaps in the biology of THCs that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

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

Cited by 25 publications

References 213 publications

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Tumor Hybrid Cells: Nature and Biological Significance

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