Cancer Stem Cells: Impact, Heterogeneity, and Uncertainty

Abstract

The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…In particular, cell sorting methods lack standardisation. Moreover, the use of flow cytometry is not ideal because by lack of gold standard, investigators use different markers [55][56][57]. Moreover, there is still a debate regarding the best method for culturing GSCs.…”

Cancer stem cell definitions and terminology: the devil is in the details

“…As a result, the tumour may initially appear to be eliminated, but it later reappears because the rarer and grossly invisible populations of CSCs have survived. In addition to the inherent insensitivity of some CSCs to currently used anticancer drugs, continuing genomic and epigenomic changes are believed to confer new treatment-resistant properties that are then passed on to daughter generations of CSCs and their progeny [5][6][7][8][9] . Interactions of CSCs with their microenvironment (CSC niches) may also contribute to an ability to resist treatment [9][10][11][12][13] .…”

“…This powerful strategy has been successfully applied to the detection of CSCs in many types of human cancers [1][2][3][4]9,12 . Sphere formation in non-adherent cultures has been used as a surrogate in vitro method for detecting CSCs from some primary human tumours [14][15][16][17][18] .…”

Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells

“…In most cases, they are referred to as tumor-initiating cells (TICs). The existence of CSC population remains a controversial topic due to questions about the robustness of CSC markers (Magee et al, 2012), however, three independent studies successfully identified and tracked CSCs in brain, skin and intestinal tumors of mice Driessens et al, 2012;Schepers et al, 2012). These findings might provide further evidence to support that CSCs are the driving force of tumor development (Gilbertson and Graham, 2012).…”