High expression of VEGF and PI3K in glioma stem cells provides new criteria for the grading of gliomas

Wang, Lei; Zhang, Luyao; Weigao, Shen; Liu, Yanbo; Luo, Yan

doi:10.3892/etm.2015.2906

Cited by 11 publications

(8 citation statements)

References 52 publications

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“…Elevated levels of vascular endothelial growth factors (VEGFs) are expressed by endothelial cells involved in angiogenesis and bone marrow-derived progenitor cells, and moreover, many types of human cancer cells can also secrete VEGFs (Kerbel, 2008). Evidence from different studies indicates that CSCs show greater potential for tumor initiation, generation, and production of higher levels of VEGFs than the non-stem cells in cancer population, thus exhibiting more potent proangiogenic capability (Ping & Bian, 2011; Wang et al, 2016). CSCs with elevated VEGF levels are typical example for the significance of angiogenesis in tumor progression (Ojha et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model

Alhawarat

Hammad

Hijjawi

et al. 2019

PeerJ

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BackgroundBreast cancer is the most common type of cancer among females. Hypoxia mediates cancer hallmarks and results from reduced oxygen level due to irregularities in tumor vascularization or when the tumor size prevents oxygen diffusion and triggers angiogenesis to compensate for low oxygen. Cancer stem cells (CSCs) are a rare subpopulation, able to self-renew and to give rise to tumor-initiating cells. It is proposed that CSCs’ secretions help to recruit endothelial cells via angiogenic factors to establish tumor vascularization. In the tumor microenvironment, the effect of hypoxia on CSCs and the impact of their secretions on triggering angiogenesis and tumor vascularization remain questionable. In this study, three-dimensional (3D) CSCs derived from MCF-7 were directly exposed to repetitive long-term cycles of hypoxia to assess its effect on CSCs and then to evaluate the role of the hypoxic CSCs’ (CSCsHYP) secretions in angiogenesis using (HUVECs) as a model for tumor neovascularization response.MethodsCSCs derived from MCF-7 cell-line were expanded under repetitive, strictly optimized, long-term/continuous and intermittent hypoxic shots for almost four months to assess hypoxic effect on CSCs, sorted based on CD44+/CD24− biomarkers. Hypoxic phenotype of CSCsHYP was evaluated by assessing the acquired chemoresistance using MTT assay and elevated stemness properties were assessed by flow cytometry. To evaluate the effect of the secretions from CSCsHYP on angiogenesis, HUVECs were exposed to CSCsHYP conditioned-medium (CdM)—in which CSCs had been previously grown—to mimic the tumor microenvironment and to assess the effect of the secretions from CSCsHYP on the HUVECs’ capability of tube formation, migration and wound healing. Additionally, co-culture of CSCsHYP with HUVECs was performed.ResultsCSCsHYP acquired higher chemoresistance, increased stemness properties and obtained greater propagation, migration, and wound healing capacities, when compared to CSCs in normoxic condition (CSCsNOR). HUVECs’ tube formation and migration abilities were mediated by hypoxic (CSCs) conditioned media (CdM).DiscussionThis study demonstrates that chemoresistant and migrational properties of CSCs are enhanced under hypoxia to a certain extent. The microenvironment of CSCsHYP contributes to tumor angiogenesis and migration. Hypoxia is a key player in tumor angiogenesis mediated by CSCs.

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Section: Introductionmentioning

confidence: 99%

The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model

Alhawarat

Hammad

Hijjawi

et al. 2019

PeerJ

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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 can be observed in Figure 2 K–O, frequently in nestin + blood vessels, IQGAP1 + /Iba1 + cells were observed in close proximity to the vessel wall (arrowhead).…”

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

IJMS

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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 onco-biology 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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“…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 can be observed in Figure 2K Figure S3).…”

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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High expression of VEGF and PI3K in glioma stem cells provides new criteria for the grading of gliomas

Cited by 11 publications

References 52 publications

The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model

The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model

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

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