IL‐1β microenvironment promotes proliferation, migration, and invasion of human glioma cells

Hurmath, K. Fathima; Ramaswamy, Palaniswamy; Nandakumar, Dalavaikodihalli Nanjaiah

doi:10.1002/cbin.10353

Cited by 62 publications

(40 citation statements)

References 37 publications

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“…IL-1b, one member of the IL-1 family, is a proinflammatory cytokine in cancer pathogenesis 26 . IL-1b stimulation promotes U87-MG cell viability and proliferation 27 . Aberrant expression of IL-1b by GBM cells influenced the migratory capacity, unique gene signature, and proinflammatory signaling 28, 29 .…”

Section: Discussionmentioning

confidence: 99%

Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA/mRNA regulatory network analysis

Chen

Hsi

et al. 2017

Sci Rep

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The insulin-like growth factor (IGF)-1 signaling is relevant in regulating cell growth and cytokine secretions by glioblastomas. MicroRNAs determine the cell fate in glioblastomas. However, relationships between IGF-1 signaling and miRNAs in glioblastoma pathogenesis are still unclear. Our aim was to validate the IGF-1-mediated mRNA/miRNA regulatory network in glioblastomas. Using in silico analyses of mRNA array and RNA sequencing data from The Cancer Genome Atlas (TCGA), we identified 32 core enrichment genes that were highly associated with IGF-1-promoted cytokine-cytokine receptor interactions. To investigate the IGF-1-downregulated miRNA signature, microarray-based approaches with IGF-1-treated U87-MG cells and array data in TCGA were used. Four miRNAs, including microRNA (miR)-9-5p, miR-9-3p, miR-181d, and miR-130b, exhibited an inverse correlation with IGF-1 levels. The miR-181d, that targeted the most IGF-1-related cytokine genes, was significantly reduced in IGF-1-treated glioma cells. Statistical models incorporating both high-IGF-1 and low-miR-181d statuses better predicted poor patient survival, and can be used as an independent prognostic factor in glioblastomas. The C-C chemokine receptor type 1 (CCR1) and interleukin (IL)-1b demonstrated inverse correlations with miR-181d levels and associations with patient survival. miR-181d significantly attenuated IGF-1-upregulated CCR1 and IL-1b gene expressions. These findings demonstrate a distinct role for IGF-1 signaling in glioma progression via miR-181d/cytokine networks.

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Section: Discussionmentioning

confidence: 99%

Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA/mRNA regulatory network analysis

Chen

Hsi

et al. 2017

Sci Rep

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“…Glioblastoma (GBM) is the most common malignant primary brain tumor with devastating proliferative and invasive characteristics; its aggressive growth pattern led GBM patients face a poor prognosis even after having received the best available treatment modalities12342829. However, the distinct biological behavior of aggressive proliferation and invasive growth of GBM might be the unexplored therapeutic targets for treatment of this fatal tumor5.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer cell migration and invasion resulted in the diffuse and invasive growth of glioblastoma, which makes it difficult to eradicate GBM for conventional therapeutics345. A mesenchymal phenotype is the biological character of GBM, GBM cells often obtain the ability to migrate, invade and metastasize through epithelial-to-mesenchymal transition (EMT)1343536.…”

Section: Discussionmentioning

confidence: 99%

“…Despite current progresses in therapeutic modalities for GBM, such as surgery, radiotherapy and chemotherapy, the outcome for GBM patients remains dismal; the recurrence is inevitable, invasive growth is a major cause of the high mortality of GBM123. The malignant tumor cells are characterized with unlimited proliferation, migration and invasion potential4; the diffuse invasion of GBM enables it to escape complete surgical resection and chemo- and radiation therapy, which is a major obstacle to eradicate GBM45. Moreover, glioblastomas are resistant to chemotherapy, radiation and other adjuvant therapies, no effective therapy is then available currently67.…”

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confidence: 99%

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Kukoamine A inhibits human glioblastoma cell growth and migration through apoptosis induction and epithelial-mesenchymal transition attenuation

Wang

Sun

et al. 2016

Sci Rep

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Cortex lycii radicis is the dried root bark of Lycium chinense, a traditional Chinese herb used in multiple ailments. The crude extract of Cortex lycii radicis has growth inhibition effect on GBM cells. Kukoamine A (KuA) is a spermine alkaloid derived from it. KuA possesses antioxidant, anti-inflammatory activities, but its anticancer activity is unknown. In this study, the growth and migration inhibition effect of KuA on human GBM cells and the possible mechanism of its activity were investigated. After KuA treatment, proliferation and colony formation of GBM cells were decreased significantly; apoptotic cells were increased; the cell cycle was arrested G0/G1 phase; the migration and invasion were decreased, the growth of tumors initiated from GBM cells was inhibited significantly; the expressions of 5-Lipoxygenase (5-LOX) were decreased, apoptotic proteins, Bax and caspase-3 were increased, and antiapoptotic protein Bcl-2 was decreased significantly; The expressions of CCAAT/enhancer binding protein β (C/EBPβ), N-cadherin, vimentin, twist and snail+slug were decreased significantly, while the expression of E-cadherin was increased significantly in KuA treated GBM cells and tumor tissues. KuA inhibited human glioblastoma cell growth and migration in vitro and in vivo through apoptosis induction and epithelial-mesenchymal transition attenuation by downregulating expressions of 5-LOX and C/EBPβ.

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“…TNF‐α and IL‐1β activate the production of IL‐6 and IL‐8, and these pro‐tumorigenic mediators promote the growth of GBM (Yeung et al, ). Moreover, our previous study has highlighted the role of IL‐1β in the invasion of glioma cells (Fathima Hurmath et al, ).…”

Section: Introductionmentioning

confidence: 96%

TNF‐α mediated MEK–ERK signaling in invasion with putative network involving NF‐κB and STAT‐6: a new perspective in glioma

Ramaswamy

Goswami

Nanjaiah

et al. 2019

Cell Biology International

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Glioblastoma is the most common malignant primary brain tumor with poor prognosis. Invasion involves pro-inflammatory cytokines and major signaling hubs. Tumor necrosis factor-α (TNF-α) acts as a master switch in establishing an intricate link between inflammation and cancer. The present study attempted to explore the possible implication of MAPK extracellular signaling-regulated kinase kinase (MEK)-extracellular signaling-regulated kinase (ERK) signaling pathway and expression of nuclear factor-κB (NF-κB), signal transducers and activators of transcription-6 (STAT-6), ERK, and phosphorylated-ERK (p-ERK) signaling proteins in TNF-α microenvironment. U0126 and PD98059 were used to inhibit the MEK-ERK1/2 pathway. TNF-α stimulation enhanced invasion in U87MG, U251MG and patient-derived primary glioma cells, whereas cell viability was not altered. Matrix metalloproteinase-2 (MMP-2) activity was increased only in U251MG glioma cells. These data suggest that TNF-α microenvironment plays an important role in the invasion of U251MG, U87MG, and patient-derived primary glioma cells, without any cytotoxic effect. The MMP-2 activity is differentially regulated by TNF-α stimulation in these cells. TNF-α stimulation upregulated the protein expression of ERK-1, ERK-2 and also increased the level of p-ERK1/2. TNF-α stimulation further upregulated the expression of NF-κB1, STAT-6 in tandem with Ras-MEK signaling system in U87MG cells, which emphasized the possible involvement of these signaling hubs in the glioma microenvironment. MEK-ERK inhibitors significantly attenuated the invasion of U87MG cells mediated by the TNF-α stimulation, probably through their inhibitory impact on p-ERK1/2 and ERK-2. This study provides the possible rationale of invasion by glioma cells in a TNF-α-induced proinflammatory milieu, which involves direct role of MEK-ERK signaling, with possible implication of NF-κB and STAT-6.

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IL‐1β microenvironment promotes proliferation, migration, and invasion of human glioma cells

Cited by 62 publications

References 37 publications

Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA/mRNA regulatory network analysis

Identification of IGF-1-enhanced cytokine expressions targeted by miR-181d in glioblastomas via an integrative miRNA/mRNA regulatory network analysis

Kukoamine A inhibits human glioblastoma cell growth and migration through apoptosis induction and epithelial-mesenchymal transition attenuation

TNF‐α mediated MEK–ERK signaling in invasion with putative network involving NF‐κB and STAT‐6: a new perspective in glioma

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