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Cancer stem cells in solid tumors

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, CA 94304, United States.
Current Opinion in Biotechnology (Impact Factor: 8.04). 11/2007; 18(5):460-6. DOI: 10.1016/j.copbio.2007.10.007
Source: PubMed

ABSTRACT Cancer stem cells (CSCs) are cells that drive tumorigenesis, as well as giving rise to a large population of differentiated progeny that make up the bulk of the tumor, but that lack tumorigenic potential. CSCs have been identified in a variety of human tumors, as assayed by their ability to initiate tumor growth in immunocompromised mice. Further characterization studies have demonstrated that gene expression profiles in breast cancer correlate with patient prognosis, and brain CSCs are specifically resistant to radiation through DNA damage repair. In addition, specific signaling pathways play a functional role in CSC self renewal and/or differentiation, and early studies indicate that CSCs are associated with a microenvironmental niche. Thus the biological properties of CSCs are just beginning to be revealed, and the continuation of these studies should lead to the development of CSC-targeted therapies for cancer treatment.

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    • "As in many types of solid cancers, diversity of glioma may be a consequence of genetic changes, clonal evolution, different environment, and the existence of a cellular hierarchy in which a minority of stem-like cells generate nontumorigenic more differentiated cells [4]. The Tumor Initiating Cell (TIC) model of cancer development and progression states that tumors, like normal adult tissues, contain a subset of cells characterized by three main properties: (1) self-renewal, this is, the capacity to produce more TICs, so they can maintain tumor growth indefinitely; (2) differentiation, since they give rise to differentiated progeny thereby generating all the various cell types that comprise the tumor, and (3) TICs are capable of initiating tumor growth in vivo [5] [6]. In the field of glial tumors, they are referred to as glioma initiating cells (GICs), and they were among the first solid tumor TICs described [7] [8]. "
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    • "Moreover, CSCs are also resistant to chemotherapy and radiation and may be, as normal SCs are, protected against various insults, likely by mechanisms such as quiescence, expression of ATP binding cassette (ABC) pumps which may lead to multidrug resistance, high expression of anti-apoptotic proteins and resistance to DNA damage [37] [38] [39]. Unfortunately, CSC-rich tumors are associated with aggressive disease and poor prognosis [40] emphasizing the importance of unraveling their biology and the need to develop means to combat them. CSC may arise from the transformation of a normal ASC or progenitor cell. "
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    FEBS letters 02/2014; 588(16). DOI:10.1016/j.febslet.2014.02.011 · 3.34 Impact Factor
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    • "Neoplasia Vol. 16, No. 2, 2014 Cisplatin and Cancer Stem Cells Nör et al. 143 CSCs are resilient cells that play a major role in resistance to chemotherapy and radiotherapy in several tumor types [41] [42] [43]. For example, a relatively quiescent subpopulation of glioma cells with CSC properties was implicated in tumor regrowth after treatment of glioblastomas with temozolomide [13]. "
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    ABSTRACT: Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs). These unique cells, named here cancer stem cells (CSCs), proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6)] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B) cells and observed that cisplatin treatment increased (P = .0013) the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDH(high)CD44(high))]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDH(high)CD44(high) immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation (indicative of stemness) was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK) phosphorylation (indicative of differentiation processes) was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs and suggest a mechanism for resistance to cisplatin therapy in head and neck cancer.
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