Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

Melzer, Catharina; Ohe, Juliane von der; Luo, Tianjiao; Hass, Ralf

doi:10.3390/ijms22115930

Cited by 19 publications

(18 citation statements)

References 70 publications

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“…In most cases investigated cancer-cell fusion has been associated with altered tumor progression, with the assumption that cancer hybrids are more metastatic and resistant to cancer therapy than the parental cells (for review see [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]). Moreover, fused cancer cells can display tumor dormancy [ 120 ].…”

Section: Therapeutic and Clinical Consequences Of Cancer-cell Fusionmentioning

confidence: 99%

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Hass

Ohe

Dittmar

2021

Cancers

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Fusion of cancer cells either with other cancer cells (homotypic fusion) in local vicinity of the tumor tissue or with other cell types (e.g., macrophages, cancer-associated fibroblasts (CAFs), mesenchymal stromal-/stem-like cells (MSC)) (heterotypic fusion) represents a rare event. Accordingly, the clinical relevance of cancer-cell fusion events appears questionable. However, enhanced tumor growth and/or development of certain metastases can originate from cancer-cell fusion. Formation of hybrid cells after cancer-cell fusion requires a post-hybrid selection process (PHSP) to cope with genomic instability of the parental nuclei and reorganize survival and metabolic functionality. The present review dissects mechanisms that contribute to a PHSP and resulting functional alterations of the cancer hybrids. Based upon new properties of cancer hybrid cells, the arising clinical consequences of the subsequent tumor heterogeneity after cancer-cell fusion represent a major therapeutic challenge. However, cellular partners during cancer-cell fusion such as MSC within the tumor microenvironment or MSC-derived exosomes may provide a suitable vehicle to specifically address and deliver anti-tumor cargo to cancer cells.

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Section: Therapeutic and Clinical Consequences Of Cancer-cell Fusionmentioning

confidence: 99%

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Hass

Ohe

Dittmar

2021

Cancers

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“…Likewise, cell fusion plays an important role during pathophysiological conditions including tumor development. Thus, cancer cell fusion with macrophages [8][9][10][11] or mesenchymal stroma-/stem-like cells [12][13][14] can result in tumor reduction [15], tumor promotion [16], or tumor dormancy [17,18].…”

Section: Introductionmentioning

confidence: 99%

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Dittmar

Weiler

Luo

et al. 2021

Cancers

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Cell fusion is a well-known, but still scarcely understood biological phenomenon, which might play a role in cancer initiation, progression and formation of metastases. Although the merging of two (cancer) cells appears simple, the entire process is highly complex, energy-dependent and tightly regulated. Among cell fusion-inducing and -regulating factors, so-called fusogens have been identified as a specific type of proteins that are indispensable for overcoming fusion-associated energetic barriers and final merging of plasma membranes. About 8% of the human genome is of retroviral origin and some well-known fusogens, such as syncytin-1, are expressed by human (cancer) cells. Likewise, enveloped viruses can enable and facilitate cell fusion due to evolutionarily optimized fusogens, and are also capable to induce bi- and multinucleation underlining their fusion capacity. Moreover, multinucleated giant cancer cells have been found in tumors derived from oncogenic viruses. Accordingly, a potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion will be summarized in this review.

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“…Labeled DNA was applied to the array with hybridization buffer and human Cot-1 DNA (Thermo Scientific, Waltham, MA, USA). Array slides were incubated for 24 h at 65 • C. After washing and scanning the arrays, images were analyzed with Feature Extraction software v10.7.3.1 (Agilent Technologies, Santa Clara, CA, USA) [23]. Probe mapping was conducted according to its genomic location in the UCSC genome browser (human NCBI37/hg19).…”

Section: Microarray-based Comparative Genomic Hybridization (Acgh) Assaymentioning

confidence: 99%

Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5

et al. 2022

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a highly selective and promising anticancer agent due to its specific apoptosis-inducing effect on tumor cells, rather than most normal cells. TRAIL is currently under investigation for use in the treatment of leukemia. However, the resistance of leukemic cells to TRAIL-induced apoptosis may limit its efficacy. The mechanisms of leukemic cell resistance to antitumor immunity remains a topical issue. In this work, we have found an increase in the resistance to TRAIL-induced cell death in human leukemia THP-1 cells, which was caused by differentiation into a macrophage-like phenotype in high-density culture in vitro. Stressful conditions, manifested by the inhibition of cell growth and the activation of cell death in high-density culture of THP-1 cells, induced the appearance of cells adhered to culture dishes. The THP-1ad cell line was derived by selection of these adhered cells. The genetic study, using STR and aCGH assays, has shown that THP-1ad cells were derived from THP-1 cells due to mutagenesis. The THP-1ad cells possessed high proliferative potential and a macrophage-like immunophenotype. The adhesion of THP-1ad cells to the extracellular matrix was mediated by αVβ5 integrin. The cytokine production, as well as the rise of intracellular ROS and NO activities by LPS in THP-1ad cell culture, were characteristic of macrophage-like cells. The THP-1ad cells were found to appear to increase in resistance to TRAIL-induced cell death in comparison with THP-1 cells. The mechanism of the increase in TRAIL-resistance can be related to a decrease in the expression of death receptors DR4 and DR5 on the THP-1ad cells. Thus, the macrophage-like phenotype formation with the maintenance of a high proliferative potential of leukemic cells, caused by stress conditions in high-density cell cultures in vitro, can induce an increase in resistance to TRAIL-induced cell death due to the loss of DR4 and DR5 receptors. The possible realization of these events in vivo may be the reason for tumor progression.

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Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

Cited by 19 publications

References 70 publications

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5

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