Abstract
BackgroundCancer 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.MethodsAfter 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.ResultsOur 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.ConclusionsAltogether these results indicate that the combination of CS/ICs properties and genomic rearrangement in hybrids is likely to be key to tumour progression.
Highlights
Cancer stem/Initiating cell (CS/IC) hypothesis argues that cancer stem/initiating cells (CS/ICs) are responsible of tumour initiation, drug resistance, metastasis or disease relapse
Fused cells exhibit ALDHhigh activity immediately after cell fusion As previously described [22], hybrid cell lines (H1 to H4) were established after spontaneous cell fusion of E6E7 (IMR90 immortalized with E6 and E7) and RST (IMR90 transformed with E6, E7, RAS, Smallt and hTERT)
Cell populations with high aldehyde dehydrogenase (ALDH) activity has been detected in many sarcoma histotypes and enabled the identification of CS/ICs [25,26,27]
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. We described that fusion leads to hybrids with metastatic capacity This process triggered genomic rearrangements in hybrid cells together with increased metastasis development. Gast et al recently identified hybrids in the blood of Tumours present heterogeneous cancer cell population with genetic and phenotypic differences. To explain this diversity, many models were established. A second model, described a hierarchical organisation of tumours, where cancer stem/initiating cells (CS/ICs) are at the top of the
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