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Review
. 2022 Feb 15:10:814714.
doi: 10.3389/fcell.2022.814714. eCollection 2022.

Tumor Hybrid Cells: Nature and Biological Significance

Maria S Tretyakova  1 , Ayalur R Subbalakshmi  2 , Maxim E Menyailo  1 , Mohit Kumar Jolly  2 , Evgeny V Denisov  1
Affiliations
Review

Tumor Hybrid Cells: Nature and Biological Significance

Maria S Tretyakova et al. Front Cell Dev Biol. .

Abstract

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.

Keywords: cancer; cell fusion; drug resistance; metastasis; tumor hybrid cell.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The proposed life cycle of tumor hybrid cells. Different factors trigger the fusion of cancer and normal cells. Most hybrid cells die, and only a few can reach distant organs. These hybrid cells can enter a state of dormancy or form metastases.
FIGURE 2
FIGURE 2
Types of tumor hybrid cells.
FIGURE 3
FIGURE 3
Potential therapeutic targets in tumor hybrid cells. TLR4, toll-like receptor 4; MMP9, matrix metalloproteinase 9; Wnt/β-catenin, signaling pathway; Nanog, transcription factor.
See this image and copyright information in PMC

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