Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

Peng, Xiaochun; Zhang, Min; Meng, Yingying; Liang, Yuanxin; Wang, Yingying; Liu, Xiaoqin; Cai, Wen-Qi; Zhou, Yang; Wang, Xianwang; Ma, Zhaowu; Xiang, Ying; Zeng, Li‐Si; Cui, Shuzhong; Yang, Liuming; Xin, Hong‐Wu

doi:10.3892/or.2021.8096

Cited by 9 publications

(4 citation statements)

References 83 publications

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“…The COVID-19 pandemic drew attention to the connection between pathogens, cancer, and neuropsychiatric disorders, suggesting the possibility of common treatment strategies ( Xu et al., 2020 ). For example, TMEM16F inhibitor niclosamide and its analogs nitazoxanide, hexachlorophene and dichlorophen, present with intriguing anthelmintic, anticancer, and anti-ALS properties, indicating similar pathogenesis ( Peng et al., 2021 ). Indeed, as these agents target S100A4, a protein involved in schizophrenia and inhibited by the phenothiazine class of antipsychotic drugs, a common pathogenetic mechanism is being highlighted ( Malashkevich et al., 2010 ; D’Ambrosi et al., 2021 ).…”

Section: Treatment Strategies For Pathological Cell-cell Fusionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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Section: Treatment Strategies For Pathological Cell-cell Fusionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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“…These macrophage–tumor cell hybrids display increased capacities to evade immunity and migrate [ 7 , 8 , 9 ]. We and others have demonstrated that tumor stem cells and monocytes/macrophages with an M2 phenotype are those more prone to generate tumor hybrid cells (THC) [ 6 , 10 ]. The importance of the cellular interaction between tumor cells and TAMs in BC has been substantiated by the observation of dense tumor cells with strong immunoreactivity with the endocytic receptor for haptoglobin–hemoglobin complexes (CD163, which is characteristic of M2 polarized macrophages) in BC tumor biopsies [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells’ Pluripotency in Bladder Cancer

Rubio

Avendaño-Ortíz

Ruiz-Palomares

et al. 2022

Cancers

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Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects. The overexpression of histone deacetylases (HDACs) in BC has been correlated with macrophage polarization together with higher tumor grades and poor prognosis. Herein we demonstrated that phenylbutyrate acid (PBA), a HDAC inhibitor, acts as an antitumoral compound and immunomodulator. In BC cell lines, PBA induced significant cell cycle arrest in G1, reduced stemness markers and increased PD-L1 expression with a corresponding reduction in histone 3 and 4 acetylation patterns. Concerning its role as an immunomodulator, we found that PBA reduced macrophage IL-6 and IL-10 production as well as CD14 downregulation and the upregulation of both PD-L1 and IL-1β. Along this line, PBA showed a reduction in IL-4-induced M2 polarization in human macrophages. In co-cultures of BC cell lines with human macrophages, a double-positive myeloid–tumoral hybrid population (CD11b+EPCAM+) was detected after 48 h, which indicates BC cell–macrophage fusions known as tumor hybrid cells (THC). These THC were characterized by high PD-L1 and stemness markers (SOX2, NANOG, miR-302) as compared with non-fused (CD11b−EPCAM+) cancer cells. Eventually, PBA reduced stemness markers along with BMP4 and IL-10. Our data indicate that PBA could have beneficial properties for BC management, affecting not only tumor cells but also the TME.

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“…Cell–cell fusion is a common phenomenon related to physiological processes such as fertilization and tissue repair in which the two lipid bilayer membranes from two cells merge into one. It is known that cancer cells can also fuse with other cells such as leukocytes, fibroblasts, and macrophages (heterotypic cell fusion), as well as with other cancer cells (homotypic fusion) [ 40 , 41 ]. Cell fusion originates bi- or multinucleated cells harboring particular cell attributes of both parent cells.…”

Section: Discussionmentioning

confidence: 99%

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

Castillo¹,

Anract

Delongchamps

et al. 2023

Cancers

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Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target.

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Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

Cited by 9 publications

References 83 publications

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells’ Pluripotency in Bladder Cancer

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

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