Stem cells in cancer: instigators and propagators?

Abstract

SummaryThere is growing realization that many -if not all -cancer-cell populations contain a subpopulation of self-renewing stem cells known as cancer stem cells (CSCs). Unlike normal adult stem cells that remain constant in number, CSCs can increase in number as tumours grow, and give rise to progeny that can be both locally invasive and colonise distant sites -the two hallmarks of malignancy. Immunodeficient mouse models in which human tumours can be xenografted provide persuasive evidence that CSCs are present in human leukaemias and many types of solid tumour. In addition, many studies have found similar subpopulations in mouse tumours that show enhanced tumorigenic properties when they are transplanted into histocompatible mice. In this Commentary, we refer to CSCs as tumour-propagating cells (TPCs), a term that reflects the assays that are currently employed to identify them. We first discuss evidence that cancer can originate from normal stem cells or closely related descendants. We then outline the attributes of TPCs and review studies in which they have been identified in various cancers. Finally, we discuss the implications of these findings for successful cancer therapies.Key words: Clonogenicity, Immunodeficient mice, Self-renewal, Stem cells, Tumour-propagating cells Journal of Cell Science Small intestineIn the mouse small intestine there is both a slowly cycling stem cell population found ~4-5 cell positions above the base of the crypt (Sangiorgi and Capecchi, 2008), and a rapidly cycling stem cell population composed of slender-shaped cells [so-called crypt base columnar cells (CBCCs)] that are sandwiched between Paneth cells at the base of the crypt (Barker et al., 2007). The stem cell characteristics of the two compartments have been established using elegant genetic-lineage tracking techniques. The former cell population expresses Bmi1, a component of the polycombrepressing complex 1 (PRC1) that prevents stem cell senescence; this Bmi1-expressing population can give rise to clones that contain all intestinal lineages. CBCCs, by contrast, express the Wnt target gene Lgr5, which encodes an orphan G-protein-coupled receptor (Barker and Clevers, 2010); these Lgr5-expressing cells are also multipotential stem cells (Barker et al., 2007). Targeted deletion of the tumour suppressor gene Apc (adenomatous polyposis coli) in Lgr5-expressing CBCCs resulted in rapidly growing adenomas, whereas targeted deletion of Apc in the higher-positioned TACs that are the direct descendants of either stem cell population failed to induce substantial adenoma growth (Barker et al., 2009). These data illustrate that a mutation in a stem cell population is most effective for tumour initiation in the short term. However, small adenomas derived from TACs persisted for nearly a year in this model, so the possibility that cancer later arises from these adenomas cannot be excluded, particularly given the fact that human colorectal cancers grow very slowly (Camplejohn et al., 1973). Intriguingly, 36 days after induction of th...

Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

“…Numerous studies have demonstrated that only a small subpopulation of tumor cells in malignant tissues, termed cancer stem cells (CSCs) or tumor initiating cancer cells (TICs), has the capacity to regenerate the original tumor and to maintain the heterogeneity of tumor tissues in animal models (20,21). Studies conducted by O'Brien et al (22) and Ricci-Vitian et al (23), demonstrated that CD133 + cells, but not CD133 -cells, derived from human colon carcinomas, initiated tumor development in immunodeficient mice, and exhibited properties of CSCs.…”

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

“…Independently of the possible origin of CSC in somatic stem cells (Alison et al, 2010), the use of this denomination implies some explicit but also implicit assumptions, varying from one author to another, that we and others have previously analyzed (Shackleton et al, 2009;Dirks, 2010;Maenhaut et al, 2010;Roesch et al, 2010;Shackleton, 2010). To avoid misconceptions, we and others have proposed to call such cells 'tumor-propagating cells' (TPCs) in agreement with their operational demonstration by xenografts (Kelly et al, 2007;Hong et al, 2008;Maenhaut et al, 2010).…”

“…A detailed list of various CSC-TPC markers in different cancers can be found in Alison et al, (2010). We first briefly summarize our previous extensive analysis of the concept (Maenhaut et al, 2010) adding a few very recent informations.…”

Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia

“…This differentiation process is characterized by changes in cell morphology, adhesiveness, and expression of megakaryocytic markers as well as cell growth arrest [24,38]. In the present study, when K562 cells were treated with PMA at high concentration for long time, the colony forming activity of K562 cells could be completely suppressed, indicating that the clonogenicity, which is highly correlated with tumorigenicity [3,6], would be suppressed by inducing differentiation in chronic myelogenous leukemic cells.…”

“…1 B and C). These results demonstrate that induction of differentiation can inhibit colony-forming activity in soft agar, which is highly correlated with tumorigenicity [3,6].…”