The role of interleukin‑6‑STAT3 signalling in glioblastoma (Review)

West, Alice J.; Tsui, Vanessa; Stylli, Stanley S.; Nguyen, Huy; Morokoff, Andrew; Kaye, Andrew H.; Luwor, Rodney B

doi:10.3892/ol.2018.9227

Cited by 67 publications

(67 citation statements)

References 122 publications

(124 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, to test for a possible contribution of the STAT family of transcription factors, we assessed STAT3 activity. STAT3 has been previously reported as deregulated in GBM TAM and associated with expression of anti‐inflammatory cytokines, contributing to an immunosuppressed TME (Wu et al , ; West et al , ). Moreover, it has been shown to regulate the inflammatory activity of monocytes in response to infection in an mTOR‐dependent manner (Weichhart et al , ).…”

Section: Resultsmentioning

confidence: 99%

Microglia promote glioblastoma via mTOR‐mediated immunosuppression of the tumour microenvironment

et al. 2020

View full text Add to dashboard Cite

Tumour‐associated microglia/macrophages (TAM) are the most numerous non‐neoplastic populations in the tumour microenvironment in glioblastoma multiforme (GBM), the most common malignant brain tumour in adulthood. The mTOR pathway, an important regulator of cell survival/proliferation, is upregulated in GBM, but little is known about the potential role of this pathway in TAM. Here, we show that GBM‐initiating cells induce mTOR signalling in the microglia but not bone marrow‐derived macrophages in both in vitro and in vivo GBM mouse models. mTOR‐dependent regulation of STAT3 and NF‐κB activity promotes an immunosuppressive microglial phenotype. This hinders effector T‐cell infiltration, proliferation and immune reactivity, thereby contributing to tumour immune evasion and promoting tumour growth in mouse models. The translational value of our results is demonstrated in whole transcriptome datasets of human GBM and in a novel in vitro model, whereby expanded‐potential stem cells (EPSC)‐derived microglia‐like cells are conditioned by syngeneic patient‐derived GBM‐initiating cells. These results raise the possibility that microglia could be the primary target of mTOR inhibition, rather than the intrinsic tumour cells in GBM.

show abstract

Section: Resultsmentioning

confidence: 99%

Microglia promote glioblastoma via mTOR‐mediated immunosuppression of the tumour microenvironment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…RPS6 expression in GBM is partially regulated by IL‐6, which in turn is associated with inflammation 40,41 . Furthermore, IL‐1β is secreted from macrophages at border niches, 7 and inflammation due to IL‐1β potentially influences RPS6 expression.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal protein S6 promotes stem‐like characters in glioma cells

et al. 2020

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans‐differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high‐grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA‐mediated RPS6 knock‐down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC‐predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence.

show abstract

“…Signal transducer and activator of transcription (STAT) 3 is a member of the family of transcription factors that is involved in the transmission of extracellular signals into the nucleus, thereby influencing the transcription of various genes. In carcinogenesis, STAT3 upregulates genes that can promote tumor survival, angiogenesis, resistance to cell death, and cell cycle progression [166]. Upregulation of STAT3 in GBM has been demonstrated in numerous studies, as reviewed by Kim et al [167].…”

Section: Resveratrol and Stat3 Signalingmentioning

confidence: 99%

The Plant-Derived Compound Resveratrol in Brain Cancer: A Review

et al. 2020

View full text Add to dashboard Cite

Despite intensive research, malignant brain tumors are among the most difficult to treat due to high resistance to conventional therapeutic approaches. High-grade malignant gliomas, including glioblastoma and anaplastic astrocytoma, are among the most devastating and rapidly growing cancers. Despite the ability of standard treatment agents to achieve therapeutic concentrations in the brain, malignant gliomas are often resistant to alkylating agents. Resveratrol is a plant polyphenol occurring in nuts, berries, grapes, and red wine. Resveratrol crosses the blood‒brain barrier and may influence the central nervous system. Moreover, it influences the enzyme isocitrate dehydrogenase and, more importantly, the resistance to standard treatment via various mechanisms, such as O6-methylguanine methyltransferase. This review summarizes the anticancer effects of resveratrol in various types of brain cancer. Several in vitro and in vivo studies have presented promising results; however, further clinical research is necessary to prove the therapeutic efficacy of resveratrol in brain cancer treatment.

show abstract

The role of interleukin‑6‑STAT3 signalling in glioblastoma (Review)

Cited by 67 publications

References 122 publications

Microglia promote glioblastoma via mTOR‐mediated immunosuppression of the tumour microenvironment

Microglia promote glioblastoma via mTOR‐mediated immunosuppression of the tumour microenvironment

Ribosomal protein S6 promotes stem‐like characters in glioma cells

The Plant-Derived Compound Resveratrol in Brain Cancer: A Review

Contact Info

Product

Resources

About