Genome remodeling upon mesenchymal tumor cell fusion contributes to tumor progression and metastatic spread

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

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Acquisition of Metastatic Properties via Somatic Cell Fusion: Implications for Tumor Progression in Vivo

New Experimental Modalities in the Control of Neoplasia ◽

10.1007/978-1-4684-5242-6_3 ◽

1986 ◽

pp. 41-55 ◽

Cited By ~ 9

Author(s):

Patrick De Baetselier ◽

Ed Roos ◽

Hendrik Verschueren ◽

Steven Verhaegen ◽

Daniel Dekegel ◽

...

Keyword(s):

Tumor Progression ◽

Somatic Cell ◽

Cell Fusion ◽

Somatic Cell Fusion

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Carbonic anhydrase IX enhances tumor cell proliferation and tumor progression in osteosarcoma

OncoTargets and Therapy ◽

10.2147/ott.s177605 ◽

2018 ◽

Vol Volume 11 ◽

pp. 6879-6886 ◽

Cited By ~ 6

Author(s):

Kazuma Okuno ◽

Takao Matsubara ◽

Tomoki Nakamura ◽

Takahiro Iino ◽

Takuya Kakimoto ◽

...

Keyword(s):

Cell Proliferation ◽

Carbonic Anhydrase ◽

Tumor Cell ◽

Tumor Progression ◽

Carbonic Anhydrase Ix ◽

Tumor Cell Proliferation

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Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

PLoS ONE ◽

10.1371/journal.pone.0014816 ◽

2011 ◽

Vol 6 (6) ◽

pp. e14816 ◽

Cited By ~ 32

Author(s):

Fang Zong ◽

Eleni Fthenou ◽

Filip Mundt ◽

Tünde Szatmári ◽

Ilona Kovalszky ◽

...

Keyword(s):

Cell Adhesion ◽

Tumor Cell ◽

Mesenchymal Tumor ◽

Tumor Cell Adhesion ◽

And Migration

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Dendritic Cell-Tumor Cell Fusion Vaccines

Advances in Experimental Medicine and Biology - Cell Fusion in Health and Disease ◽

10.1007/978-94-007-0763-4_11 ◽

2011 ◽

pp. 177-186 ◽

Cited By ~ 3

Author(s):

Walter T. Lee

Keyword(s):

Dendritic Cell ◽

Tumor Cell ◽

Cell Fusion ◽

Cell Tumor

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Tumor Microenvironment and Cell Fusion

BioMed Research International ◽

10.1155/2019/5013592 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Erhui Jiang ◽

Tinglin Yan ◽

Zhi Xu ◽

Zhengjun Shang

Keyword(s):

Tumor Microenvironment ◽

Tumor Cell ◽

Tumor Cells ◽

Cell Fusion ◽

Direct Interaction ◽

Tumor Stem Cell ◽

Migration And Invasion ◽

Future Research ◽

Microenvironmental Factors ◽

Cell Cell

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.

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Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype

Frontiers in Immunology ◽

10.3389/fimmu.2020.594775 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ren-Hui Chen ◽

Zhi-Wen Xiao ◽

Xiao-Qing Yan ◽

Ping Han ◽

Fa-Ya Liang ◽

...

Keyword(s):

Cell Migration ◽

Tumor Cell ◽

Tumor Progression ◽

Cytotoxic T Lymphocyte ◽

Tumor Stage ◽

Advanced Tumor Stage ◽

Tumor Cell Migration ◽

Advanced Tumor ◽

Interferon Stimulated Gene 15 ◽

Small Molecular Inhibitors

Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15+ CD163+ TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15+ CD163+ macrophages inhibited antitumor CD8+ cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.

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Treatment-Induced Tumor Cell Apoptosis and Secondary Necrosis Drive Tumor Progression in the Residual Tumor Microenvironment through MerTK and IDO1

Cancer Research ◽

10.1158/0008-5472.can-18-1106 ◽

2018 ◽

Vol 79 (1) ◽

pp. 171-182 ◽

Cited By ~ 12

Author(s):

Thomas A. Werfel ◽

David L. Elion ◽

Bushra Rahman ◽

Donna J. Hicks ◽

Violeta Sanchez ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Cell ◽

Tumor Progression ◽

Cell Apoptosis ◽

Residual Tumor ◽

Tumor Cell Apoptosis ◽

Secondary Necrosis

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Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans

eLife ◽

10.7554/elife.08005 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 4

Author(s):

Mor Levi-Ferber ◽

Hai Gian ◽

Reut Dudkevich ◽

Sivan Henis-Korenblit

Keyword(s):

Tumor Cell ◽

Er Stress ◽

Tumor Progression ◽

Tumor Cells ◽

Tumor Therapy ◽

Tumor Model ◽

Apoptosis Resistance ◽

Stress Sensor ◽

C Elegans ◽

Cell Transdifferentiation

Deciphering effective ways to suppress tumor progression and to overcome acquired apoptosis resistance of tumor cells are major challenges in the tumor therapy field. We propose a new concept by which tumor progression can be suppressed by manipulating tumor cell identity. In this study, we examined the effect of ER stress on apoptosis resistant tumorous cells in a Caenorhabditis elegans germline tumor model. We discovered that ER stress suppressed the progression of the lethal germline tumor by activating the ER stress sensor IRE-1. This suppression was associated with the induction of germ cell transdifferentiation into ectopic somatic cells. Strikingly, transdifferentiation of the tumorous germ cells restored their ability to execute apoptosis and enabled their subsequent removal from the gonad. Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery.

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