Ailles L, Weissman I.. Cancer stem cells in solid tumors. Curr Opin Biotechnol 18: 460-466
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.
- SourceAvailable from: Nilson Anselmo
- "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 . 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  . 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  . "
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- "Evolving research indicates that cancer stem cells (CSC) are a potential driving force of tumor initiation and progression due to their self-renewal and unlimited proliferative capacity [27,28]. The existence of CSC was reported in human cancers, including brain, breast, bone marrow, prostrate, colon, and lung [29,30]. "
ABSTRACT: Background Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. Methods Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 μg/cm2 surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. Results We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24low and CD133high that are associated with SWCNT-induced CSC formation and tumorigenesis. Conclusions Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles.Particle and Fibre Toxicology 05/2014; 11(1):22. DOI:10.1186/1743-8977-11-22 · 7.11 Impact Factor
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- "Evolving research in stem cells and cancer biology have provided strong evidence for the existence of cancer stem cells (CSCs) in various human solid tumors, including brain, breast, bone marrow, prostrate, colon, and lung [3,4]. These CSCs are potential driving force of tumor initiation and progression due to their self-renewal and tumorigenic properties [5,6]. Induction of CSCs from non-tumorigenic cells may initiate carcinogenesis. "
ABSTRACT: Cancer stem cells (CSCs) may represent targets for carcinogenic initiation by chemical and environmental agents. Recent studies have raised a concern over the potential carcinogenicity of carbon nanotubes (CNTs), one of the most commonly used engineered nanomaterials with asbestos-like properties. Here, we show that chronic (6-month) exposure of human lung epithelial cells to single-walled (SW) CNTs at the workplace-relevant concentration induced an emergence of lung CSCs, as indicated by the induction of CSC tumor spheres and side population (SP). These CSCs, which were found to overexpress tumor promoter caveolin-1 (Cav-1), displayed aggressive cancer phenotypes of apoptosis resistance and enhanced cell invasion and migration compared with their non-CSC counterpart. Using gene manipulation strategies, we reveal for the first time that Cav-1 plays an essential role in CSC regulation and aggressiveness of SWCNT-transformed cells partly through p53 dysregulation, consistent with their suggested role by microarray and gene ontology analysis. Cav-1 not only promoted tumorigenesis in a xenograft mouse model but also metastasis of the transformed cells to neighboring tissues. Since CSCs are crucial to the initiation and early development of carcinogenesis, our findings on CSC induction by SWCNTs and Cav-1 could aid in the early detection and risk assessment of the disease.Oncotarget 05/2014; 5(11). DOI:10.18632/oncotarget.1956 · 6.36 Impact Factor