Induced Pluripotent Stem Cells Derived From Tumor Cells

Induced pluripotent stem cells (iPSCs) can be generated from various differentiated cell types by the expression of a set of defined transcription factors. This technology provides a major breakthrough to overcome potential hurdles for the applications of human embryonic stem cell for scientific studies and medical treatment.In2006, Yamanaka and James Thomson successfully generated iPS cells from mouse somatic cells by the expression of defined transcriptional factors. In2010Rudolf Jaenisch and Thijn R.Brummelkamp described the gerenation of iPS cells derived from human chronic myeloid leukemia. So far, no report regarding iPS cells generated from solid tumor cells has been published.We generated the B16-F10-2B2-iPS cells from mouse melanoma B16-F10-2B2cell line using a piggyBac transposon and tetracycline regulated expression of iPS transciption factors (Oct4, Sox2, c-Myc and Klf4). Our results showed that transfection efficiency was0.1%, and efficiency of generating tumor-derived iPS-like cells morphologically similar to iPS cells was1.0%. Further analysis indicated that these cells expressed ES/iPS cell specific genes, such as Rex-1, Nanog and Oct-4. However, they also exhibited properties different from ES cells or iPS cells, such as weak alkaline phosphatase staining. We further characterized the biological properties of this tumor-derived iPS cells, including growth, differentiation, tumor formation and metastasis in mice.Our results showed that there are multiple stages from solid tumor cells to iPS cells. Solid tumor cells may require additional intrinsic and extrinsic factors for complete conversion to iPS cells. Our model system provides a valuable tool for further analysis and characterization of molecular mechanisms regulating the tumorigenesis, stem cell and differentiation.