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 20 publications

(18 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 20 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

Contact Info

Product

Resources

About