Cancer Stem Cells (CSCs) in melanoma: There's smoke, but is there fire?

Abstract

Cancer stem cells (CSCs), also called Tumor Initiating Cells (TICs), can be defined as cancer cells that are present within solid tumors or hematological cancers, which have characteristics associated with normal stem cells, but which can give rise to all cell types found in a particular cancer sample. CSCs, therefore, are transformed stem cells, which can self-renew, differentiate into diverse progenies, and drive continuous tumor growth (Kreso & Dick, , Cell Stem Cell, 14:275-291; Schatton et al., , Nature, 451:345-349; Villani, Sabbatino, Ferrone, & Ferrone, , Melanoma Management, 2:109-114; Zhou et al., , Drug Discovery, 8:806-823) (Fig. ). [Figure: see text].

Keywords: humanized mice; innate and adaptive immunity; phenotypic plasticity; tumor initiating cells.

Figure 1

Figure 2

Experimental Approach to Investigate CSC Properties in the Context of Genetic Sub-clones. Studying CSCs will require separation of distinct genetic sub-clones, because CSCs cannot be reliably identified in genetically heterogeneous tumors. One method by which sub-clones can be separated is by transplanting cancer cells at clonal cell doses over multiple recipients. Following engraftment of the human cancer cells, the hierarchical composition of a particular sub-clone can be studied using prospective purification of cells. Sequential transplantations of cancer cells allows for the tracking of further clonal evolution. For solid tumors, sampling different geographical regions from the primary tumor will be important for capturing distinct sub-clones. (From Kreso and Dick, 2014)

Figure 3

Immunologic characteristics of animal model systems commonly used in melanoma research. NK: Natural killer; NOD: Nonobese diabetic; NSG: NOD-scid IL2rγnull ; SCID: Severe combined immunodeficiency. Melanoma. (From Villani et al. 2015).