Cell fusion is an important event that mediates various biological processes. However, the role of cell fusion in cancer has not been very well described due to technical limitations. Here we describe a Cre-Lox recombination model system to study spontaneous heterotypic cell-cell fusion between tumor and non-tumor cells. This fusion event results in hybrid cells that are hyperploid and contain DNA from both parental cells. In addition, fusion-derived hybrids eventually adopt cancer gene profile, are more resistant to chemotherapy, and show increased tumorsphere-forming capacity. This model system can therefore be used to further our understanding of cell-cell fusion in the context of cancer.
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