Acquisition of cancer stem cell capacities after spontaneous cell fusion

Cancer stem/Initiating cell (CS/IC) hypothesis argues that CS/ICs are responsible of tumour initiation, drug resistance, metastasis or disease relapse. Their detection in several cancers supports this concept. However, their origin is still misunderstood. Cell fusion is shown to take part in the for...

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Bibliographic Details
Published in:BMC cancer 2021-03, Vol.21 (1), p.241-241, Article 241
Main Authors: Merle, Candice, Lagarde, Pauline, Lartigue, Lydia, Chibon, Frédéric
Format: Article
Language:English
Subjects:
Cancer cells
Cancer stem cells
Carcinogenesis - pathology
Care and treatment
Cell Fusion
Cell hybridization
Cell Line, Tumor
Cellular Reprogramming
Complications and side effects
Genetic aspects
Genotype
Health aspects
Humans
Hybrid Cells
Life Sciences
Mesenchymal Stem Cells - pathology
Metastasis
Neoplasms - pathology
Neoplastic Stem Cells - pathology
Risk factors
Sarcoma
Spheroids, Cellular
Stem cells
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Summary:Cancer stem/Initiating cell (CS/IC) hypothesis argues that CS/ICs are responsible of tumour initiation, drug resistance, metastasis or disease relapse. Their detection in several cancers supports this concept. However, their origin is still misunderstood. Cell fusion is shown to take part in the formation of CS/ICs, i.e. fusion between mesenchymal stem cell and cancer cell. In a previous paper, we described that fusion leads to hybrids with metastatic capacity. This process triggered genomic rearrangements in hybrid cells together with increased metastasis development. Here, we hypothesize that cell fusion could be strong enough to provoke a cellular reprogramming and the acquisition of CS/IC properties, promoting metastasis formation. After spontaneous cell fusion between E6E7 (IMR90 with the oncogenes E6 and E7) and RST (IMR90 fully transformed) cell lines, hybrid cells were selected by dual antibiotic selection. Cancer stem cells capacities were evaluated regarding capacity to form spheres, expression of stem cell markers and the presence of ALDHhigh cells. Our data show that after cell fusion, all hybrids contain a percentage of cells with CS/ICs properties, regarding. Importantly, we lastly showed that NANOG inhibition in H1 hybrid decreases this migration capacity while having no effect on the corresponding parental cells. Altogether these results indicate that the combination of CS/ICs properties and genomic rearrangement in hybrids is likely to be key to tumour progression.
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-021-07979-2