Overexpression of STAT1 suppresses angiogenesis under hypoxia by regulating VEGF‑A in human glioma cells

Zhang, Yunsheng; Jin, Guishan; Zhang, Junwen; Mi, Ruifang; Zhou, Yiqiang; Fan, Wenhua; Cheng, Sen; Song, Wenjie; Zhang, Bo; Ma, Mengjiao; Liu, Fusheng

doi:10.1016/j.biopha.2018.05.079

Cited by 30 publications

(29 citation statements)

References 29 publications

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“…As future approaches, a possible co-administration of ZIKV BR and immune checkpoint inhibitors targeting PD-1, STAT1, and CCR2, found overexpressed in both Boxer and Dachshund tumors tissues, could enhance the anti-tumoral immune response. 29,30 In the present study, our data suggest a general trend in the establishment of a prevalent cytokine/chemokine cluster led by increase of IL-8, KC-like, and MCP-1 at serum and CFS samples. It confirms the evolution of the inflammatory response after ZIKV BR administration since these cytokines and chemokines constitute a family of secretory proteins that drive and control leukocyte migration.…”

Section: Discussionsupporting

confidence: 62%

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Kaid

Madi²,

Astray

et al. 2020

Molecular Therapy

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Malignant brain tumors are among the most aggressive cancers with poor prognosis and no effective treatment. Recently, we reported the oncolytic potential of Zika virus infecting and destroying the human central nervous system (CNS) tumors in vitro and in immunodeficient mice model. However, translating this approach to humans requires pre-clinical trials in another immunocompetent animal model. Here, we analyzed the safety of Brazilian Zika virus (ZIKV BR) intrathecal injections in three dogs bearing spontaneous CNS tumors aiming an anti-tumoral therapy. We further assessed some aspects of the innate immune and inflammatory response that triggers the anti-tumoral response observed during the ZIKV BR administration in vivo and in vitro. For the first time, we showed that there were no negative clinical side effects following ZIKV BR CNS injections in dogs, confirming the safety of the procedure. Furthermore, the intrathecal ZIKV BR injections reduced tumor size in immunocompetent dogs bearing spontaneous intracranial tumors, improved their neurological clinical symptoms significantly, and extended their survival by inducing the destruction specifically of tumor cells, sparing normal neurons, and activating an immune response. These results open new perspectives for upcoming virotherapy using ZIKV to destroy and induce an anti-tumoral immune response in CNS tumors for which there are currently no effective treatments.

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Section: Discussionsupporting

confidence: 62%

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Kaid

Madi²,

Astray

et al. 2020

Molecular Therapy

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“…However, hypoxia's tumorpromoting effects were reversed after PLOD1 knockout, suggesting that PLOD1 is an important downstream gene of the tumor-promoting effects under hypoxic environment on GSCs. Thus, hypoxia due to rapid glioma growth can activate HIF-1 [52], promoting the proliferation, invasion, and anti-apoptosis of GSCs through transcriptional regulation of PLOD1, leading to a series of malignant behaviors [53,54]. Also, it may be possible that PLOD1, together with HIF-1, constitutes a positive loop of malignancy in GSCs, which in turn induces MES transition and radiotherapy tolerance in GBM.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced PLOD1 overexpression contributes to the malignant phenotype of glioblastoma via NF-κB signaling

et al. 2021

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Procollagen lysyl hydroxylase 1 (PLOD1) is highly expressed in malignant tumors such as esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer. Bioinformatics analysis revealed that PLOD1 is associated with the progression of GBM, particularly the most malignant mesenchymal subtype (MES). Moreover, in the TCGA and CGGA datasets, the mean survival time of patients with high PLOD1 expression was significantly shorter than that of patients with low expression. The clinical samples confirmed this result. Therefore, we aimed to investigate the effect of PLOD1 on the development of mesenchymal GBM in vitro and in vivo and its possible mechanisms. Molecular experiments were conducted on the patient-derived glioma stem cells and found that PLOD1 expressed higher in tumor tissues and cancer cell lines of patients with GBM, especially in the MES. PLOD1 also enhanced tumor viability, proliferation, migration, and promoted MES transition while inhibited apoptosis. Tumor xenograft results also indicated that PLOD1 overexpression significantly promotes malignant behavior of tumors. Mechanistically, bioinformatics analysis further revealed that PLOD1 expression was closely associated with the NF-κB signaling pathway. Besides, we also found that hypoxic environments also enhanced the tumor-promoting effects of PLOD1. In conclusion, overexpression of PLOD1 may be an important factor in the enhanced invasiveness and MES transition of GBM. Thus, PLOD1 is a potential treatment target for mesenchymal GBM or even all GBM.

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“…As a transcription factor, we found that HIF-1 can directly upregulate the expression of LBH under hypoxia. Hypoxia and active capillary endothelial proliferation are typical features of high-grade gliomas [36]. The frequent hypoxia caused by the rapid growth of tumors can activate HIF-1 [36,37], which can promote the proliferation, migration and angiogenesis of gliomas and the self-renewal of GSCs [36,38,39], and even possibly lead to the transcription and expression of LBH.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Limb-Bud and Heart (LBH) promotes angiogenesis in human glioma via VEGFA-mediated ERK signalling under hypoxia

et al. 2019

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Background: Glioma is the most common primary malignant tumor in the central nervous system with frequent hypoxia and angiogenesis. Limb-Bud and Heart (LBH) is a highly conserved transcription cofactor that participates in embryonic development and tumorigenesis. Methods: The conditioned media from LBH regulated human glioma cell lines and patient-derived glioma stem cells (GSCs) were used to treat the human brain microvessel endothelial cells (hBMECs). The function of LBH on angiogenesis were examined through methods of MTS assay, Edu assay, TUNEL assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment. Findings: Our study found for the first time that LBH was overexpressed in gliomas and was associated with a poor prognosis. LBH overexpression participated in the angiogenesis of gliomas via the vascular endothelial growth factor A (VEGFA)-mediated extracellular signal-regulated kinase (ERK) signalling pathway in human brain microvessel endothelial cells (hBMECs). Rapid proliferation of gliomas can lead to tissue hypoxia and hypoxia inducible factor-1 (HIF-1) activation, while HIF-1 can directly transcriptionally regulate the expression of LBH and result in a self-reinforcing cycle. Interpretation: LBH may be a possible treatment target to break the vicious cycle in glioma treatment.

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Overexpression of STAT1 suppresses angiogenesis under hypoxia by regulating VEGF‑A in human glioma cells

Cited by 30 publications

References 29 publications

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

Hypoxia-induced PLOD1 overexpression contributes to the malignant phenotype of glioblastoma via NF-κB signaling

Overexpression of Limb-Bud and Heart (LBH) promotes angiogenesis in human glioma via VEGFA-mediated ERK signalling under hypoxia

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