Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

doi:10.3389/fsurg.2016.00021

Cited by 206 publications

(283 citation statements)

References 235 publications

(299 reference statements)

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Section: Resultsmentioning

confidence: 99%

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Rotoli

Pérez-Rodríguez

Morales

et al. 2017

Preprint

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Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the oncobiology of GBM, we performed immunohistochemical confocal microscopic analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1 + staining was observed in neurons (Map2 + cells), in cancer stem cells (CSC; nestin + ) and in several macrophages (CD31 + or Iba1 + ). Our results indicate that the IQGAP1 protein is involved in normal cell physiology as well as oncologic processes.

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Section: Resultsmentioning

confidence: 99%

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Rotoli

Pérez-Rodríguez

Morales

et al. 2017

Preprint

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“…To further characterize IQGAP1 + cells, the intermediate filament protein nestin was used as a marker of neural stem/progenitor cells in GBM [21][22][23][24][25][26] in combination with Iba1. As it can be observed in Figure 2 In many IQGAP1 and Iba1 colocalizing cells, a more intense staining for these proteins was found and in a polarized manner, close to nuclei, drawing an image resembling the actin-ring core of podosomes/invadopodia ( Figure 3I-L, thin arrow).…”

Section: Resultsmentioning

confidence: 99%

“…Our labelling with specific antibodies identified cells around and within vessels as CSCs or GSCs (nestin + /IQGAP1 + ), Tumor Associated Macrophages (TAMs) and endothelial cells (CD31 + /IQGAP1 + ), microglia (Iba1 + /CD31 − /IQGAP1 + ) and, in addition to these well characterized kind of cells, colonies of IQGAP1 + /Iba1 + /nestin + cells are found surrounding nestin + cells (Figure 2K-O). An increasing number of studies has recently provided evidences supporting the Hierarchical Cancer Stem Cell Model, which postulates that tumours are composed of biologically distinct cell classes with different functional abilities and behaviour [24][25][26]34]. One of the hints of this model is the distinction between stem cells and progenitor cells, which differ in terms of hierarchy and biology.…”

Section: Iqgap1 In Gbm Astrocytes and Gscsmentioning

confidence: 99%

“…Stem cells are multipotent and with a high self-renewal capacity, while progenitor cells have a restricted differentiation potential and a limited self-renewal capacity. In this contest it has been observed that nestin protein is expressed not only in GSCs, but also further down in the stem cell hierarchy as it's expressed in more differentiated cells (progenitor cells) as well [25,26,34]. The observed IQGAP1 + /Iba1 + /nestin + cells could represent a common ancestor for TAMs and GBM tumorigenic neural precursors and/or, probably, an interconvertible multipotent progenitor cell form of both kinds and/or glioblastoma amplifying cancer cells [33] (GSCs or progenitor cells).…”

Section: Iqgap1 In Gbm Astrocytes and Gscsmentioning

confidence: 99%

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IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Rotoli¹,

Pérez-Rodríguez²,

Morales³

et al. 2017

Preprint

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Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signalling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumours, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopical analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1 + staining was observed in neurons (Map2 + cells), in cancer stem cells (CSC; nestin + ) and in several macrophages (CD31 + or Iba1 + ). Our results indicate that the IQGAP1 protein is involved in normal cell physiology and also in oncologic processes.

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“…Dissecting the role of GSCs through whole-tissue analyses faces a number of methodological challenges mainly due to their rarity and non-homogeneous distribution within the tumour [57]. Furthermore, the relative number of GSCs undergoes dynamic changes during tumour progression [58,59]; last not least there is persistent uncertainty about GSCs markers [56,60]. A plethora of putative markers of GSC has been implicated in the past decade but their prognostic value remains uncertain.…”

Section: Molecular Stratification Of Recurrent Glioblasoma: Challengementioning

confidence: 99%

Assessment of Anti-Proliferative Activities of Selected Medicinal Plant Extracts Used for Management of Diseases around Lake Victoria Basin

Swaya¹,

Aduma²,

Chelimo³

et al. 2017

J Carcinog Mutagen

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Glioblastoma is the most common and most malignant type of intrinsic brain tumor in adults. The standard of care for glioblastoma consists of surgical debulking followed by combined radiochemotherapy. The clinical efficacy of standard therapies for newly diagnosed glioblastomas is rather modest with the highest survival rate at 5-years being less than 10%. Inevitable recurrence after cytotoxic therapies poses the major challenge in the clinical management of high grade gliomas. For recurrent glioblastomas, there is no standard therapy with lack of level one evidence for treatment efficacy. Recent evidence indicates that post-therapy recurrence in gliomas is a consequence of a plethora of molecular and cellular factors including intratumoural heterogeneity, functional hierarchy of distinct types of glioma cells, dynamic changes in the molecular landscapes and cellular composition of the tumour during therapy and the impact of particular treatment modalities. There is an emerging consensus that molecular distinctions within and between individual tumours is an important factor determining clinical outcomes. Consequently, integrated approaches based on the combination of molecular profiling with traditional methods such as immunohistochemical phenotyping, karyotyping and/or non-quantitative methylation-specific PCR have emerged as a promising venue towards increasing the predictive value of diagnostics for malignant brain tumors. The high level of inter-and intra-tumoural molecular diversity in gliomas underscores the need of integrating high throughput molecular profiling and pharmacogenomics into a diagnostic paradigm for gliomas and raises the possibility that molecular-instructed personalized treatments may provide clinical benefit to patients with glioblastoma, particularly in the setting of post-treatment recurrence. Here we discuss potential prospects and challenges of patient-tailored diagnostics and personalized treatment strategies for recurrent glioblastomas.

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Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

Cited by 206 publications

References 235 publications

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

Assessment of Anti-Proliferative Activities of Selected Medicinal Plant Extracts Used for Management of Diseases around Lake Victoria Basin

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