Cancer stem cells: an evolving concept

Abstract

The cancer stem cell (CSC) concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are typically rare. This idea is not new, but has recently gained prominence because of advances in defining normal tissue hierarchies, a greater appreciation of the multistep nature of oncogenesis and improved methods to propagate primary human cancers in immunodeficient mice. As a result we have obtained new insights into why the CSC concept is not universally applicable, as well as a new basis for understanding the complex evolution, phenotypic heterogeneity and therapeutic challenges of many human cancers.

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

“…However, as yet, in no instance has a profile been identified that can reliably replace functional assays for normal stem cells. It should also be noted that many of the phenotypic markers found to be empirically useful for isolating particular subsets of cells in unperturbed normal tissue have proved to be functionally dispensable or differently regulated when they are activated in vivo or in vitro 3,4 . In addition, there is increasing evidence that normal tissue stem cells that are identified by their tissue-regenerative activity in different assays may fail to include cells with similar latent potentialities that are only revealed under different conditions.…”

“…Not surprisingly, what is meant by the term CSC has evolved over that period. Historically, it first invoked the concept that malignant cell populations are organized as unidirectional cellular hierarchies in which CSCs constitute biologically unique subsets of cells, which are distinguished from the bulk of the cells that they produce by their exclusive ability to perpetuate the growth of a malignant cell population indefinitely [1][2][3][4] . This concept is of considerable clinical importance because it emphasizes the crucial need to target CSCs to achieve cures.…”

“…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] .…”

“…descendant stem cells with tissue-maintaining potential. This paradigm was first established in the haematopoietic system in mice and humans and has since been extended to many other tissues in both species 3 . Interestingly, it has also become apparent that even stringently defined normal tissue stem cells with extensive self-renewal properties can be intrinsically heterogeneous with regard to their differentiation and selfrenewal control in different sites or stages of development [19][20][21] .…”

A double blinded, placebo-controlled pilot study to examine reduction of CD34+/CD117+/CD133+ lymphoma progenitor cells and duration of remission induced by neoadjuvant valspodar in dogs with large B-cell lymphoma

“…The importance of tumor-propagating cells in the pathogenesis of cancer is becoming increasingly well recognized 1 . However, there are only a few reports supporting the existence of such cells in human lymphoma cell lines or in transgenic lymphoma mouse models 2– 5 .…”