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The Hallmarks of Circulating Hybrid Cells

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Syncytia: Origin, Structure, and Functions

Abstract

While tumor metastases represent the primary driver of cancer-related mortality, our understanding of the mechanisms that underlie metastatic initiation and progression remains incomplete. Recent work identified a novel tumor-macrophage hybrid cell population, generated through the fusion between neoplastic and immune cells. These hybrid cells are detected in primary tumor tissue, peripheral blood, and in metastatic sites. In-depth analyses of hybrid cell biology indicate that they can exploit phenotypic properties of both parental tumor and immune cells, in order to intravasate into circulation, evade the immune response, and seed tumors at distant sites. Thus, it has become increasingly evident that the development and dissemination of tumor-immune hybrid cells play an intricate and fundamental role in the metastatic cascade and can provide invaluable information regarding tumor characteristics and patient prognostication. In this chapter, we review the current understanding of this novel hybrid cell population, the specific hallmarks of cancer that these cells exploit to promote cancer progression and metastasis, and discuss exciting new frontiers that remain to be explored.

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Abbreviations

CHCs:

Circulating hybrid cells

CTCs:

Circulating tumor cells

EMT:

Epithelial to mesenchymal transition

EpCAM:

Epithelial cellular adhesion molecule

FISH:

Fluorescence in situ hybridization

GFP:

Green fluorescent protein

GVHD:

Graft versus host disease

MET:

Mesenchymal to epithelial transition

MMP:

Matrix metalloproteinase

PBMCs:

Peripheral blood mononuclear cells

RFP:

Red fluorescent protein

TAMs:

Tumor-associated macrophages

VEGF:

Vascular endothelial growth factor

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Correspondence to Melissa H. Wong .

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© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

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Patel, R.K. et al. (2024). The Hallmarks of Circulating Hybrid Cells. 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_21

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