Lessons from common markers of tumor-initiating cells in solid cancers

Abstract

Tumor-initiating cells (TICs) have emerged as the driving force of carcinomas, which appear as hierarchically structured. TICs as opposed to the tumor bulk display tumor forming potential, which is linked to a certain degree of self-renewal and differentiation, both major features of stem cells. Markers such as CD44, CD133, CD24, EpCAM, CD166, Lgr5, CD47, and ALDH have been described, which allow for the prospective enrichment of TICs. It is conspicuous that the same markers allow for an enrichment of TICs in various entities and, on the other hand, that different combinations of these markers were independently reported for the same tumor entity. Potential functions of these markers in the regulation of TIC phenotypes remained somewhat neglected although they might give insights in common molecular themes of TICs. The present review discusses major TIC markers with respect to their function and potential contributions to the tumorigenic phenotype of TICs.

EpCAM and its potential role in tumor-initiating cells

“…7,11,62 Uncontrolled activation of these and other pathways are presumed to play essential roles in the initial formation of TICs and therefore in tumorigenesis in general. 14,63 As these pathways are frequently involved in the regulation of the phenotype of various stem cells, it is further tempting to speculate that gain-of-function mutations of members of those pathways are instrumental in the formation of TICs.…”

“…14,15 Noteworthy, some of these proteins, such as EpCAM or CD44, are expressed in an almost ubiquitous manner on most carcinoma cells and even on selected normal adult tissues, and differ primarily in their expression amplitude in TICs. Thus, combinations of several markers are more reliable to characterize cells as TICs.…”

CD133 in the Selection of Epidermal Stem Cells in Mice: Steps in the Right Direction

“…Although CD133 is a transmembrane protein of unknown function, as neither ligands nor signaling pathways have been found to associate with it, multiple lines of evidence indicate that the presence of CD133 on the cell surface may serve as a functionally relevant biomarker for carcinogenesis. For example, in a variety of tumor types including colon, pancreatic, gallbladder, ovarian, lung, glioblastoma, and melanoma, CD133 is a marker of tumor-initiating cells (TICs) that show high capacity for self-renewal, asymmetric division to propagate differentiated tumor bulk, the ability to switch between quiescent and proliferative states, and the ability for multiple rounds of tumor propagation from a single or few cells (Pardal et al, 2003;Gires, 2011). In addition, CD133 expression does appear to serve as an important prognostic factor for some cancer types (Gires, 2011).…”

Topotecan‐induced ABCG2 expression in MCF‐7 cells is associated with decreased CD24 and EpCAM expression and a loss of tumorigenicity

“…It can interact with a variety of effectors (9,10) and is involved in a multitude of regulatory mechanisms related to adhesion, cell proliferation, migration, invasiveness, and chemoresistance (8,11,12). Likewise, EpCAM, which was first described as a marker of human embryonic stem cells, is expressed on cancer cells of a variety of entities (13). In many cancer types, including breast cancer, high expression levels of EpCAM correlate with poor prognosis (14).…”

“…In many cancer types, including breast cancer, high expression levels of EpCAM correlate with poor prognosis (14). Although the functions of EpCAM as a cell adhesion molecule and promoter of cell proliferation are generally accepted, and alterations in the expression level are closely related to epithelial-mesenchymal transition during metastasis, the role of EpCAM in cancer cells is not yet completely investigated (13,15).…”