Cancer stem cell induction from mouse embryonic stem cells

Abstract

Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms.

Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs

“…iPSCs have successfully been converted into CSCs with a conditioned medium of Lewis lung carcinoma cells [21], as well as those of other cancer cell lines [20,46]. Very recently, not only iPSCs but also embryonic stem cells have been converted to CSCs in the same manner [47]. The converted CSCs exhibited the potential of self-renewal, differentiation and malignant tumorigenicity with metastasis [48].…”

Method to Convert Stem Cells into Cancer Stem Cells

“…Inject miPS-T47Dcm cells in MFP [10]. Inject miPS-PLCcm cells into the liver.Inject B6G-LLCcm cells subcutaneously [15]. …”

“…Induced pluripotent stem cells (iPSCs)/embryonic stem cells (ESCs) could acquire the characteristics of CSCs when cultured in the presence of conditioned medium (CM) prepared from various cancer cell lines without transducing foreign genes and/or mutagens [6,7,8,9,10,11,12,13,14,15]. The CSCs established from iPSCs through epigenetic regulations have been shown to have the capacity of self-renewal, differentiation, and malignant tumorigenicity.…”