Glial Progenitors as Targets for Transformation in Glioma

Ilkhanizadeh, Shirin; Lau, Jasmine; Huang, Miller; Foster, Daniel J.; Wong, Robyn A.; Frantz, Aaron; Wang, Susan; Weiss, William A.; Persson, Anders I.

doi:10.1016/b978-0-12-800249-0.00001-9

Cited by 40 publications

(32 citation statements)

References 322 publications

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“…Gliomas are tumours of the central nervous system (CNS), originating from transformed neural stem or progenitor glial cells [32]. The World Health Organisation (WHO), based on histopathological characteristics, divided gliomas into groups: low-grade gliomas (grades I and II) are benign, well-differentiated, slow-growing tumours; whereas high-grade gliomas (grades III and IV) are poorly differentiated or anaplastic, rapidly proliferating, and strongly infiltrate brain parenchyma.…”

Section: Accumulation and Functions Of Myeloid Cells In Gliomasmentioning

confidence: 99%

Myeloid-derived suppressor cells in gliomas

Gieryng¹,

Kamińska²

2016

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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors and precursors at different stages of differentiation into granulocytes, macrophages, and dendritic cells. Blockade of their differentiation into mature myeloid cells in cancer results in an expansion of this population. High-grade gliomas are the most common malignant tumours of the central nervous system (CNS), with a poor prognosis despite intensive radiation and chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed the extensive heterogeneity of immune cells infiltrating gliomas and their microenvironment. Immune cell infiltrates consist of: resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells, and T lymphocytes. Intratumoural density of glioma-associated MDSCs correlates positively with the histological grade of gliomas and patient’s survival. MDSCs have the ability to attract T regulatory lymphocytes to the tumour, but block the activation of tumour-reactive CD4+ T helper cells and cytotoxic CD8+ T cells. Immunomodulatory mechanisms employed by malignant gliomas pose an appalling challenge to brain tumour immunotherapy. In this mini-review we describe phenotypic and functional characteristics of MDSCs in humans and rodents, and their occurrence and potential roles in glioma progression. While understanding the complexity of immune cell interactions in the glioma microenvironment is far from being accomplished, there is significant progress that may lead to the development of immunotherapy for gliomas.

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Section: Accumulation and Functions Of Myeloid Cells In Gliomasmentioning

confidence: 99%

Myeloid-derived suppressor cells in gliomas

Gieryng¹,

Kamińska²

2016

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“…Glioma is the most common malignant primary brain tumor which arises from the central nervous system [1]. The tumor is highly aggressive with a mean survival time of nine to twelve months from diagnosis to death.…”

Section: Introductionmentioning

confidence: 99%

miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma

Wang

et al. 2017

Biochemical and Biophysical Research Communications

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Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3′-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3′-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma.

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“…In addition, cell cycling of CD133+ GBM cells is influenced by the tumor microenvironment (15), which also evolves in association with treatment. Recent studies have identified many alternative TPC markers in human GBM (16). The cell surface sialoglycoprotein podoplanin (PDPN) shows partial co-expression with CD133 in GBM cultures and tissues (15, 17).…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy Followed by Aurora Kinase Inhibition Targets Tumor-Propagating Cells in Human Glioblastoma

Maly

Chanthery

et al. 2015

Molecular Cancer Therapeutics

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Glioblastoma (GBM) is the most common malignant primary brain tumor. Radiotherapy fails to eliminate subpopulations of stem-like tumor-propagating cells (TPCs), resulting in tumor regrowth. To identify kinases that promote TPC self-renewal rather than increasing proliferation in human GBM cultures, we screened a library of 54 non-selective tool compounds and determined their kinase inhibitor profiles in vitro. Most compounds inhibited aurora kinase (AURK) activity and blocked TPC self-renewal, while inducing GBM cell polynucleation and apoptosis. To prevent regrowth by TPCs, we used a priming dose of radiation followed by incubation with the pan-AURK inhibitor VX680 to block self-renewal and induce apoptosis in GBM cultures. In mice xenografted with human GBM cells, radiotherapy followed by VX680 treatment resulted in reduced tumor growth and increased survival relative to either monotherapy alone or VX680 treatment prior to radiation. Our results indicate that AURK inhibition, subsequent to radiation, may enhance the efficacy of radiotherapy by targeting radioresistant TPCs in human GBMs.

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Glial Progenitors as Targets for Transformation in Glioma

Cited by 40 publications

References 322 publications

Myeloid-derived suppressor cells in gliomas

Myeloid-derived suppressor cells in gliomas

miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma

Radiotherapy Followed by Aurora Kinase Inhibition Targets Tumor-Propagating Cells in Human Glioblastoma

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