The Three-Layer Concentric Model of Glioblastoma: Cancer Stem Cells, Microenvironmental Regulation, and Therapeutic Implications
TLDR
This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk.Abstract:
Tumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called “hypoxic niche” plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development.read more
Citations
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Journal ArticleDOI
Glioblastoma: Microenvironment and Niche Concept.
TL;DR: The niche concept was originally developed to describe the location of normal neural stem cells in the subependymal layer of the sub-ventricular zone to discuss the relationship between GB stem cells (GSCs) and endothelial cells (ECs), highlighting the basic significance of the EC/tumor stem cell couple.
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BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression
Luca Persano,Francesca Pistollato,Enrico Rampazzo,A. Della Puppa,Sara Abbadi,Chiara Frasson,Francesco Volpin,Stefano Indraccolo,Renato Scienza,Giuseppe Basso +9 more
TL;DR: It is suggested that BMP2, by down-modulating the HIF-1α/MGMT axis, should increase GBM responsiveness to chemotherapy, thus opening the way to the development of future strategies for GBM treatment.
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Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion
Katyayni Vinnakota,Feng Hu,Min-Chi Ku,Petya B. Georgieva,Frank Szulzewsky,Andreas Pohlmann,Sonia Waiczies,Helmar Waiczies,Thoralf Niendorf,Seija Lehnardt,Uwe-Karsten Hanisch,Michael Synowitz,Darko Markovic,Susanne A. Wolf,Rainer Glass,Helmut Kettenmann +15 more
TL;DR: Activation of TLR2 along with TLRs 1 and/or 6 converts microglia into a glioma supportive phenotype, and evidence is found that TLR1 and TLR6 cofunction withTLR2 as heterodimers in regulating MT1-MMP expression in vitro.
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The role of cancer stem cells in glioblastoma
Swetha J. Sundar,Jason K Hsieh,Jason K Hsieh,Sunil Manjila,Justin D. Lathia,Justin D. Lathia,Justin D. Lathia,Andrew E. Sloan +7 more
TL;DR: The authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics.
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The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion
Laura Pinton,Elena Masetto,Marina Vettore,Samantha Solito,Sara Magri,Marta D’Andolfi,Paola Del Bianco,Giovanna Lollo,Jean-Pierre Benoit,Hideho Okada,Aaron Diaz,Alessandro Della Puppa,Susanna Mandruzzato +12 more
TL;DR: The infiltration by BMDM reached the highest percentages in grade IV gliomas, and it increased from the periphery to the center of the lesion, where it exerted a strong immunosuppression that was, instead, absent in the marginal area.
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