Thrombospondin‑1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma

Cui, Qi; Lei, Lei; Hu, Jinqu; Wang, Gang; Liu, Jiyuan; Ou, Shaowu

doi:10.3892/ol.2020.12283

Cited by 19 publications

(17 citation statements)

References 40 publications

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“…GBM patients. 11 The TGF-β1 8 but not the TGF-β2 12 canonical pathway transcriptionally regulates TSP1 expression through SMAD3 binding to the THBS1 promoter. TSP1 silencing inhibited cell invasion in vitro and in vivo, also in combination with anti-angiogenic therapy.…”

Section: Importance Of the Studymentioning

confidence: 99%

TGF-β promotes microtube formation in glioblastoma through thrombospondin 1

et al. 2021

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Background Microtubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs are abundant in chemoresistant gliomas, in particular glioblastomas (GBMs), while they are uncommon in chemosensitive IDH-mutant and 1p/19q co-deleted oligodendrogliomas. The aim of this study was to identify potential signaling pathways involved in MT formation. Methods Bioinformatics analysis of TCGA was performed to analyze differences between GBM and oligodendroglioma. Patient-derived GBM stem cell lines were used to investigate microtube formation under TGF-βstimulation and inhibition in vitro and in vivo in an orthotopic xenograft model. RNA sequencing and proteomics were performed to detect commonalities and differences between GBM cell lines stimulated with TGF-β Results Analysis of TCGA data showed that the TGF-β pathway is highly activated in GBMs compared to oligodendroglial tumors. We demonstrated that TGF-β1 stimulation of GBM cell lines promotes enhanced MT formation and communication via Calcium signaling. Inhibition of the TGF-β pathway significantly reduced MT formation and its associated invasion in vitro and in vivo. Downstream of TGF-β, we identified thrombospondin 1 (TSP1) as a potential mediator of MT formation in GBM through SMAD activation. TSP1 was upregulated upon TGF- β stimulation and enhanced MT formation, which was inhibited by TSP1 shRNAs in vitro and in vivo. Conclusion TGF-β and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT driven invasion/ resistance network.

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Section: Importance Of the Studymentioning

confidence: 99%

TGF-β promotes microtube formation in glioblastoma through thrombospondin 1

et al. 2021

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“…Qi C et al demonstrated that TSP-1 may be a biomarker for glioma malignancy and predict the mesenchymal subtype of GBM; they performed comprehensive bioinformatics analysis. Analyzing the correlations between THBS1 expression and immune signatures, the results reported positive correlations between THBS1 expression and Treg (a subpopulation of T cells that regulate the immune system) signatures, backing the hypothesis that THBS1 could enhance local immune tolerance in GBM [ 100 ].…”

Section: Fatty Acids Cd36 Thrombospondin-1 and Cd47 In Glioblastoma Development And Progressionmentioning

confidence: 77%

Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

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Codrici

et al. 2022

IJMS

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Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

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“…GBM is the most common malignant, high aggressive, rapid recurrent brain tumor, despite the advances in treatment [ 19 ], GBM patients also have a poor prognosis and short survival time [ 20 ]. Therefore, the novel and effective diagnostic and therapeutic molecular markers are urgent to be identified.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM)

et al. 2022

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Circular RNAs (circRNAs) are closely associated with cancer development in glioblastoma (GBM), and this study aims to explore the molecular mechanisms of a novel circular RNA circZNF652 in regulating GBM aggressiveness. The present study found that CircZNF652 and SERPINE1 were upregulated, while miR-486-5p was downregulated in GBM tissues and cell lines, and GBM patients with high expression of CircZNF652 and SERPINE1, and patients with low expression of miR-486-5p tended to have a worse prognosis. Further results validated that both silencing of circZNF652 and miR-486-5p overexpression suppressed cell growth, migration, invasion, epithelial–mesenchymal transition (EMT) and tumorigenesis in GBM cells in vitro and in vivo . Next, the underlying mechanisms were investigated, and we found that circZNF652 sponged miR-486-5p to upregulate SERPINE1 in GBM cells. Also, we validated that knock-down of circZNF652 regulated the miR-486-5p/SERPINE1 axis to reverse the malignant phenotypes in GBM cells. Interestingly, we noticed that GBM cells derived exosomes were characterized by high-expressed CircZNF652. Collectively, we concluded that targeting the circular RNA circZNF652/miR-486-5p/SERPINE1 axis was a novel and effective strategy to suppress cancer progression in GBM.

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Thrombospondin‑1 is a prognostic biomarker and is correlated with tumor immune microenvironment in glioblastoma

Cited by 19 publications

References 40 publications

TGF-β promotes microtube formation in glioblastoma through thrombospondin 1

TGF-β promotes microtube formation in glioblastoma through thrombospondin 1

Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Identification of a novel circular RNA circZNF652/miR-486-5p/SERPINE1 signaling cascade that regulates cancer aggressiveness in glioblastoma (GBM)

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