Abstract
BackgroundSeveral physiological (fertilization, placentation, wound healing) and pathophysiological processes (infection with enveloped viruses, cancer) depend on cell fusion. In cancer it was postulated that the fusion of cancer cells with normal cells such as macrophages or stem cells may not only give rise to hybrid cells exhibiting novel properties, such as an increased metastatic capacity and drug resistance, but possibly also cancer stem/ initiating cell properties. Hence, hybrid clone cells (M13HS, M13MDA435 and M13MDA231) that were derived from spontaneous fusion events of human M13SV1-EGFP-Neo breast epithelial cells and HS578T-Hyg, MDA-MB-435-Hyg and MDA-MB-231-Hyg cancer cells were investigated regarding potential in vitro cancer stem/ initiating cell properties.MethodsCD44/CD24 expression pattern and ALDH1 activity of parental cells and hybrid clones was determined by flow cytometry. A colony formation and mammosphere formation assay was applied to determine the cells’ capability to form colonies and mammospheres. Sox9, Slug and Snail expression levels were determined by Western blot analysis.ResultsFlow cytometry revealed that all hybrid clone cells were CD44+/CD24−/low, but differed markedly among each other regarding ALDH1 activity. Likewise, each hybrid clone possessed a unique colony formation and mammosphere capacity as well as unique Snail, Slug and Sox9 expression patterns. Nonetheless, comparison of hybrid clones revealed that M13HS hybrids exhibited more in vitro cancer stem/ initiating cell properties than M13MDA231 and M13MDA435 hybrids, such as more ALDH1 positive cells or an increased capacity to form colonies and mammospheres.ConclusionThe fate whether cancer stem/ initiating cells may originate from cell fusion events likely depends on the specific characteristics of the parental cells.
Highlights
Several physiological and pathophysiological processes depend on cell fusion
Injection of ID8-RFP ovary carcinoma cells into GFP mice resulted in the origin of hybrid cells that were positive for both GFP and RFP [19], which further supports the hypothesis that tumor cells and normal cells could fuse in vivo
Gast et al recently demonstrated that tumor cells obtained from female pancreatic ductal adenocarcinoma patients, which previously received a bone marrow transplant from a male donor were positive for the Y-chromosome [4] indicating that female cancer cells have fused with male bone marrow-derived cells
Summary
Several physiological (fertilization, placentation, wound healing) and pathophysiological processes (infection with enveloped viruses, cancer) depend on cell fusion. In cancer it was proposed that cell fusion might be associated with disease progression Both in vitro and in vivo data revealed that tumor cells could fuse with normal cells, such as macrophages, fibroblasts and stem cells, thereby giving rise to hybrid cells that could exhibit novel properties, such as an enhanced metastatic capacity or an increased drug resistance [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. Y-chromosome harboring pancreatic ductal adenocarcinoma hybrid cells were found in the circulation of these patients, their presence associated with a poorer prognosis [4]
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