Asbestos Cancer Update 2010

Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA. zhigang.xie@bmc.org

The results of studies conducted in the past several years have suggested that malignant brain tumors may harbor a small fraction of tumor-initiating cells that are likely to cause tumor recurrence. These cells are known as brain tumor stem cells (BTSCs) because of their multilineage potential and their ability to self-renew in vitro and to recapitulate original tumors in vivo. The understanding of BTSCs has been greatly advanced by knowledge of neural progenitor/stem cells (NPSCs), which are multipotent and self-renewing precursor cells for neurons and glia. In this article, the authors summarize evidence that genetic mutations that deregulate asymmetric cell division by affecting cell polarity, spindle orientation, or cell fate determinants may result in the conversion of NPSCs to BTSCs. In addition, they review evidence that BTSCs and normal NPSCs may reside in similar vascularized microenvironments, where similar evolutionarily conserved signaling pathways control their proliferation. Finally, they discuss preliminary evidence that mechanisms of BTSC-associated infiltrativeness may be similar to those underlying the migration of NPSCs and neurons.

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Division of Neurosurgery, University of California, San Diego, USA.

Recent advances in stem cell research and developmental neurobiology have uncovered new perspectives from which to investigate various forms of cancer. Specifically, the hypothesis that tumors consist of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the “cancer stem cell hypothesis.” The region in which this assertion is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival, and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is reviewed along with the role of tumor environment as the context within which these cells should be understood.

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Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA.

OBJECT: Brain tumor stem cells (TSCs) hypothetically drive the malignant phenotype of glioblastoma multiforme (GBM), and evidence suggests that a better understanding of these TSCs will have profound implications for treating gliomas. When grown in vitro, putative TSCs grow as a solid sphere, making their subsequent characterization, particularly the cells within the center of the sphere, difficult. Therefore, the purpose of this study was to develop a new method to better understand the proteomic profile of the entire population of cells within a sphere. METHODS: Tumor specimens from patients with confirmed GBM and glioma models in mice were mechanically and enzymatically dissociated and grown in traditional stem cell medium to generate neurospheres. The neurospheres were then embedded in freezing medium, cryosectioned, and analyzed with immunofluorescence. RESULTS: By sectioning neurospheres as thinly as 5 mum, the authors overcame many of the problems associated with immunolabeling whole neurospheres, such as antibody penetration into the core of the sphere and intense background fluorescence that obscures the specificity of immunoreactivity. Moreover, the small quantity of material required and the speed with which this cryosectioning and immunolabeling technique can be performed make it an attractive tool for the rapid assessment of TSC character. CONCLUSIONS: This study is the first to show that cryosectioning of neurospheres derived from glioma models in mice and GBM in humans is a feasible method of better defining the stem cell profile of a glioma.

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