Tumor Microenvironment and Cell Fusion.

Erhui Jiang,Zhengjun Shang,Zhi Xu,Tinglin Yan

doi:10.1155/2019/5013592

Erhui Jiang, Zhengjun Shang + Show 2 more

Open Access

https://doi.org/10.1155/2019/5013592

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Abstract

Cell fusion is a highly regulated biological process that occurs under both physiological and pathological conditions. The cellular and extracellular environment is critical for the induction of the cell–cell fusion. Aberrant cell fusion is initiated during tumor progression. Tumor microenvironment is a complex dynamic system formed by the interaction between tumor cells and their surrounding cells. Cell–cell fusion mediates direct interaction between tumor cells and their surrounding cells and is associated with tumor initiation and progression. Various microenvironmental factors affect cell fusion in tumor microenvironment and generate hybrids that acquire genomes of both parental cells and exhibit novel characteristics, such as tumor stem cell-like properties, radioresistance, drug resistance, immune evasion, and enhanced migration and invasion abilities, which are closely related to the initiation, invasion, and metastasis of tumor. The phenotypic characteristics of hybrids are based on the phenotypes of parental cells, and the fusion of tumor cells with diverse types of microenvironmental fusogenic cells is concomitant with phenotypic heterogeneity. This review highlights the types of fusogenic cells in tumor microenvironment that can fuse with tumor cells and their specific significance and summarizes the various microenvironmental factors affecting tumor cell fusion. This review may be used as a reference to develop strategies for future research on tumor cell fusion and the exploration of cell fusion-based antitumor therapies.

Highlights

Cell fusion is a process that two or more cells become one by membrane fusion [1, 2]
Cell fusion is involved in cancer stem cell formation [9, 15], high invasiveness acquisition [16], tumor microenvironment (TME) remodeling [17], epithelial–mesenchymal transition (EMT) [18], drug resistance [15], and tumor angiogenesis [19], which are closely related to the growth, invasion, and metastasis of tumor
Considering that the CCL21/ chemokine receptor 7 axis is associated with the metastasis of tumor cells to lymph nodes [56], this study suggests that cell fusion is a mechanism behind the origin of metastatic cancer cells in breast cancer

Summary

Introduction

Cell fusion is a process that two or more cells become one by membrane fusion [1, 2]. TME is always deficient in oxygen and nutrients [45] and is usually characterized by relatively low pH [35, 46] and chronic inflammatory state [47] Tumors use this relatively “harsh” environment to promote processes (e.g., cell fusion) that are related to their progression [8, 13, 48]. Hypoxia caused by oxygen deficiency, and signal pathways activated by chronic inflammation, such as matrix metalloproteinase (MMP) and tumor necrosis factor (TNF) pathways, are involved in the regulation of cell fusion [18, 44, 49, 50] These studies indicate that factors in TME are closely related to the fusion of tumor cells with tumor cells or other stromal cells. We will summarize the various factors in the TME that affect tumor cell fusion (Table 2), expecting to provide new ideas for future research on tumor cell fusion and present strategies for antitumor therapies

Tumor–Epithelial Cell Fusion

Tumor–Stromal Cell Fusion

Tumor Microenvironmental Factors Affecting Cell Fusion

Conclusion

Findings

Prospects