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Cell Fusion and Syncytia Formation in Cancer

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Syncytia: Origin, Structure, and Functions

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 71))

Abstract

The natural phenomenon of cell–cell fusion does not only take place in physiological processes, such as placentation, myogenesis, or osteoclastogenesis, but also in pathophysiological processes, such as cancer. More than a century ago postulated, today the hypothesis that the fusion of cancer cells with normal cells leads to the formation of cancer hybrid cells with altered properties is in scientific consensus. Some studies that have investigated the mechanisms and conditions for the fusion of cancer cells with other cells, as well as studies that have characterized the resulting cancer hybrid cells, are presented in this review. Hypoxia and the cytokine TNFα, for example, have been found to promote cell fusion. In addition, it has been found that both the protein Syncytin-1, which normally plays a role in placentation, and phosphatidylserine signaling on the cell membrane are involved in the fusion of cancer cells with other cells. In human cancer, cancer hybrid cells were detected not only in the primary tumor, but also in the circulation of patients as so-called circulating hybrid cells, where they often correlated with a worse outcome. Although some data are available, the questions of how and especially why cancer cells fuse with other cells are still not fully answered.

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Abbreviations

ASCT2:

Alanine serine cysteine transporter 2

BiFC:

Bimolecular fluorescence complementation

BMDC:

Bone marrow-derived cell

BMT:

Bone marrow transplantation

CAF:

Cancer-associated fibroblast

CCC:

Circulating cancer cell

CHC:

Circulating hybrid cell

CRLM:

Colorectal liver metastasis

CS/IC:

Cancer stem/initiating cell

CTC:

Circulating tumor cell

DC-STAMP:

Dendritic cell-specific transmembrane protein

DSP:

Dual split protein

DSS:

Disease-specific survival

EAC:

Esophageal adenocarcinoma

EC:

Endometrial carcinoma

FDR:

Fluorescence double reporter

g-aCTC:

Giant atypical circulating tumor cell

GFP:

Green fluorescent protein

GPI:

Glycosylphosphatidylinositol

HCC:

Hepatocellular carcinoma

HE:

Hematoxylin-eosin

HERV:

Human endogenous retrovirus

HIF-1α:

Hypoxia inducible factors-1α

HST/PR:

Heterokaryon-to-synkaryon transition/ploidy reduction

HTR2B:

5-hydroxytryptamine receptor 2B

HUVEC:

Human umbilical vein endothelial cell

IHC:

Immunohistochemistry

iMSC:

Immortalized mesenchymal stem cell

mRNA:

Messenger ribonucleic acid

MSC:

Mesenchymal stem cell

NAT:

Neoadjuvant therapy

NK cells:

Natural killer cells

NSCLC:

Non-small cell lung cancer

PANK/KRT/CK:

Pan cytokeratin

pCR:

Pathologic complete response

PGCC:

Polyploid giant cancer cell

PHSP:

Post-hybrid selection process

PS :

Phosphatidylserine

RAC:

Rectal adenocarcinoma

RANKL:

Receptor activator of NF-κB ligand

RFP:

Red fluorescent protein

RT-PCR:

Real-time polymerase chain reaction

SCC-9 :

Squamous cell carcinoma 9

shRNA:

Small hairpin ribonucleic acid

siRNA:

Small interfering ribonucleic acid

STR:

Short tandem repeat

TAM:

Tumor-associated macrophage

TMEM16:

Transmembrane member 16

UCC:

Urothelial cell carcinoma

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  1. Institute of Immunology, Center for Biomedical Education and Research (ZBAF), University of Witten/Herdecke, Witten, Germany

    Mareike Sieler & Thomas Dittmar

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  1. Mareike Sieler
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  2. Thomas Dittmar
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  1. Houston Methodist Research Institute and The Houston Methodist Hospital, Houston, TX, USA

    Malgorzata Kloc

  2. Houston Methodist Research Institute and The Houston Methodist Hospital, Houston, TX, USA

    Ahmed Uosef

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Sieler, M., Dittmar, T. (2024). Cell Fusion and Syncytia Formation in Cancer. In: Kloc, M., Uosef, A. (eds) Syncytia: Origin, Structure, and Functions. Results and Problems in Cell Differentiation, vol 71. Springer, Cham. https://doi.org/10.1007/978-3-031-37936-9_20

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