Embryonic and Cancer Stem Cells - two views of the same landscape

According to the Cancer Stem Cell (CSC) theory, there is a small subset of neoplastic cells in the tumors, which retain unlimited proliferative capacity. These cells give also rise to a differentiated cancer progeny that does not have spreading potential but makes up the bulk of the tumor. Thus, CSCs would be the ultimate cause of tumor growth, maintenance and recurrence (Figure 1). CSCs are experimentally defined by the ability to recapitulate the heterogeneity of the original tumor when transplanted into immunocompatible or nude mice. In 1867 Julius Cohnheim proposed that tumors are derived from embryonal cells that rest in the adult tissues. Later on, in the middle of the following century, Furth and Kanh (1937) and Pierce and Dixon (1959) proved the stem cell properties of a subset of cells in leukemia and testicular germ cell tumors (TGCTs) and Till and McCulloch (1961) transplanted colony forming units (CFU) from the bone marrow into lethally irradiated mice. Additionally, the group of Barry Pierce showed the in vitro modulation of cancer cell differentiation (Pierce & Verney, 1961) and the in vivo cloning of single embryonal carcinoma (EC) cells, proving their pluripotency (Kleinsmith & Pierce, 1964). The differentiation of cloned leukemic cells (Pluznik & Sachs, 1965) and the reprogramming of embryonal carcinoma (EC) cells when injected into early embryos (Brinster, 1974) were also outstanding results. All these discoveries paved the way for the isolation of embryonic stem (ES) cells (Evans and Kaufman, 1981; Martin, 1981) and one of the above groups also studied the differentiation of CSCs from distinct tumors, like squamous cell carcinoma, chondrosarcoma and adenocarcinoma (Pierce & Wallace, 1971; Pierce, 1974; Pierce et al., 1977) seeding the concept of cancer differentiation therapy (Pierce & Speers, 1988). A new progress in this matter was done with the isolation of CSCs in human acute myeloid leukemia (Lapidot et al., 1994) and, particularly, with the discovery of new markers for progenitor cells in several solid tumors, such as breast (Al-Hajj et al., 2003), brain (Singh et al., 2003) and colon (O’Brien et al., 2007) cancer. During the evolution of CSC research, there have been several technical improvements that have undoubtedly contributed to the success in the engraftment of the tumor cells in the host mice and the subsequent tumor formation. Firstly, it has been proved that the immune system of the host notably affects the survival of the transplanted cells, and thus, the use of