Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood-brain barrier

Zhao, Chen; Wang, Hongyan; Xiong, Chenghao; Liu, Yu

doi:10.1016/j.bbrc.2018.05.140

Cited by 73 publications

(58 citation statements)

References 22 publications

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“…Increased AHIF expression has been observed to be in parallel with that of VEGF (20). Furthermore, hypoxic glioblastoma releases exosomal VEGF to induce permeability of the blood-brain barrier (46).…”

Section: Discussionmentioning

confidence: 95%

“…Accumulating evidence has revealed that glioblastoma-derived exosomes contain multiple pro-angiogenic factors that induce proliferation and progression (42)(43)(44). VEGF-A has been identified to be overexpressed in hypoxic GBM-derived exosomes (45). Considering the classic function of hypoxia in angiogenesis and invasion, angiogenic genes in exosomes derived from AHIF-KD and OE cells were analyzed.…”

Section: Discussionmentioning

confidence: 99%

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AHIF promotes glioblastoma progression and radioresistance via exosomes

et al. 2018

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Glioblastoma multiforme (GBM) has the highest mortality rate among patients with brain tumors, and radiotherapy forms an important part of its treatment. Thus, there is an urgent requirement to elucidate the mechanisms conferring GBM progression and radioresistance. In the present study, it was identified that antisense transcript of hypoxia-inducible factor-1α (AHIF) was significantly upregulated in GBM cancerous tissues, as well as in radioresistant GBM cells. The expression of AHIF was also upregulated in response to radiation. Knockdown of AHIF in GBM cells decreased viability and invasive capacities, and increased the proportion of apoptotic cells. By contrast, overexpression of AHIF in GBM cells increased viability and invasive capacities, and decreased the proportion of apoptotic cells. Furthermore, exosomes derived from AHIF-knockdown GBM cells inhibited viability, invasion and radioresistance, whereas exosomes derived from AHIF-overexpressing GBM cells promoted viability, invasion and radioresistance. Further biochemical analysis identified that AHIF regulates factors associated with migration and angiogenesis in exosomes. To the best of our knowledge, the present study is the first to establish that AHIF promotes glioblastoma progression and radioresistance via exosomes, which suggests that AHIF is a potential therapeutic target for GBM.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

AHIF promotes glioblastoma progression and radioresistance via exosomes

et al. 2018

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“…61 In addition, hypoxia, a typical feature of solid tumours such as GBM, is also correlated with the disruption of the BBB. 62 Zhao et al 62 reported that exosomes derived from the hypoxic GBM cell line U87 promoted the proliferation of brain microvascular endothelial cells (BMVECs), inducing BBB permeability in an in vitro model. Changes in BBB permeability are seen within different stages of gliomas, as the progression of the disease aggravates its disruption and permeability increases.…”

Section: Current Approaches To the Management Of Gbm Diagnosismentioning

confidence: 99%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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Gliomas are the most common tumours of the central nervous system and the most aggressive form is glioblastoma (GBM). Despite advances in treatment, patient survival remains low. GBM diagnosis typically relies on imaging techniques and postoperative pathological diagnosis; however, both procedures have their inherent limitations. Imaging modalities cannot differentiate tumour progression from treatment-related changes that mimic progression, known as pseudoprogression, which might lead to misinterpretation of therapy response and delay clinical interventions. In addition to imaging limitations, tissue biopsies are invasive and most of the time cannot be performed over the course of treatment to evaluate 'real-time' tumour dynamics. In an attempt to address these limitations, liquid biopsies have been proposed in the field. Blood sampling is a minimally invasive procedure for a patient to endure and could provide tumoural information to guide therapy. Tumours shed tumoural content, such as circulating tumour cells, cell-free nucleic acids, proteins and extracellular vesicles, into the circulation, and these biomarkers are reported to cross the blood-brain barrier. The use of liquid biopsies is emerging in the field of GBM. In this review, we aim to summarise the current literature on circulating biomarkers, namely circulating tumour cells, circulating tumour DNA and extracellular vesicles as potential non-invasively sampled biomarkers to manage the treatment of patients with GBM.

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“…Vascular endothelial growth factor (VEGF) is considered to be the best-known pro-angiogenic factor, and was found to be present in GBM secreted exosomes, although the role of exosomal VEGF in the BBB opening is not fully understood [205,206]. Zhao et al, showed that GBM-secreted exosomes could induce the disruption of the BBB in laboratory studies [145]. They found that the expression of VEGF-A was up-regulated in GBM secreted exosomes in hypoxic conditions, which increased the leakiness of an in vitro BBB model via suppressing the expression of claudin-5 and occluding proteins.…”

Section: Exosomal Proteins In Gliomamentioning

confidence: 99%

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

Mahjoubin‐Tehran

Movahedpour

et al. 2020

Cell Commun Signal

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Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25 years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100 nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring.

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Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood-brain barrier

Cited by 73 publications

References 22 publications

AHIF promotes glioblastoma progression and radioresistance via exosomes

AHIF promotes glioblastoma progression and radioresistance via exosomes

Circulating biomarkers in patients with glioblastoma

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

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