It is hypothesized that KLF4 can activate p21-induced cell-cycle arrest and prevent tumor proliferation, but can also inhibit p53, blocking both cell senescence and apoptosis

It is hypothesized that KLF4 can activate p21-induced cell-cycle arrest and prevent tumor proliferation, but can also inhibit p53, blocking both cell senescence and apoptosis. into GBMs malignancy biology. and interchangeably, essentially lumping these two cell types collectively (29C34). However, the validity of this practice has been questioned (35) as progenitor cells and stem cells differ in terms of hierarchy and biology and, consequently, should be regarded as unique entities. Stem cells are multipotent with an unlimited capacity for self-renewal, whereas progenitor cells are most often unipotent with Betamethasone hydrochloride restricted capacity for self-renewal. Distinguishing between stem cells and progenitor cells in malignancy is important in the understanding of the CSC concept for carcinogenesis. However, as they presumably belong to a spectral continuum distinguishing between the two populations remains challenging. The hierarchical CSC model of malignancy proposes that a tumor arises from CSCs generated by mutations in either normal ESCs or progenitor cells, which may be present at birth or accumulated over time resulting in cells possessing the ability for Betamethasone hydrochloride uncontrolled growth and propagation (36C39). Recent studies have also observed the ability of non-CSCs to de-differentiate into CSCs due to epigenetic or environmental factors, which further increases the difficulty of tumor biology and treatment (40). Malignancy consists of a heterogeneous human population of cells, proposed to arise from CSCs. Cells inside a tumor are Betamethasone hydrochloride thought to be structured Rabbit Polyclonal to KAL1 in a similar hierarchical manner to normal tissues, ranging from probably the most primitive cells to the most adult cells (Number ?(Number4)4) (24, 41). Within a tumor, there may only be a small number of CSCs that are highly tumorigenic (Number ?(Number3B)3B) (16) and have the capacity to divide asymmetrically giving rise (1) to additional CSCs that migrate to form fresh tumors and (2) to downstream progenitor cells and differentiated malignancy cells that possess no or low tumorigenic potential (42) and form the main bulk of the tumor (38, 41, 43). It Betamethasone hydrochloride is important to notice that these two different hypotheses may not be mutually special, as clonal development has been shown to play a role in the formation of CSCs (44, 45). CSCs in Glioblastoma A combination of medical evaluation and genome-wide manifestation profiling has exposed that high-grade gliomas can be separated into four subtypes: proneural (PN), MES, neural, and proliferative (or classical) (15, 46). There remains some debate concerning the number and defining characteristics of these subtypes (46), but some criteria, such as chromosomal deletions and molecular markers (such as Notch and VEGF) have been proposed (47). The living of multiple subtypes provides another explanation for therapy resistance in GBM, which needs to be taken into account when characterizing GBM cells (7). This adds another level of difficulty to the study of GBM, as in addition to the known intra-tumoral cellular heterogeneity, there is also a degree of inter-tumor cellular heterogeneity. In addition to the tumor subtypes, CSCs isolated from high-grade gliomas will also be classified into two unique organizations: PN and MES (48, 49). Several studies have used the term glioma stem cells to describe CSCs found in GBM (40, 49, 50), but for the Betamethasone hydrochloride purpose of clearly differentiating between stem cells in lower grade gliomas and those found in GBM, this evaluate will use the term glioblastoma malignancy stem cells (GBCSCs). GBCSCs are thought to originate from either neuronal stem cells or de-differentiate from normal brain cells, such as astrocytes and oligodendrocytes (18, 40), although this de-differentiation is not universally approved (46). PN GBCSCs appear to share similarities with fetal NSCs, while MES GBCSCs more closely resemble adult NSCs (46, 51). MES GBCSCs are.