DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

García-Romero, Noemí; Carrión-Navarro, Josefa; Esteban-Rubio, Susana; Lázaro-Ibáñez, Elisa; Peris-Celda, María; Alonso, Marta M.; Guzmán-De-Villoria, Juan A; Fernández-Carballal, C.; Méndivil, Ana Ortiz de; García-Duque, Sara; Escobedo‐Lucea, Carmen; Prat-Acín, Ricardo; Belda-Iniesta, Cristóbal; Ayuso-Sacido, Ángel

doi:10.18632/oncotarget.13635

Cited by 206 publications

(175 citation statements)

References 34 publications

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“…65 Despite the association between BBB dysfunctions and GBM disease progression, EVs derived from glioma cells were shown to cross the intact BBB and were detected in the blood of GBM patients. 66 This highlights the importance of EVs in liquid biopsies since EVs can be detected in cases in which the BBB is not compromised.…”

Section: Current Approaches To the Management Of Gbm Diagnosismentioning

confidence: 93%

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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Section: Current Approaches To the Management Of Gbm Diagnosismentioning

confidence: 93%

Circulating biomarkers in patients with glioblastoma

et al. 2019

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“…Importantly, the use of EVs as therapeutic vectors presents several advantages, at least on paper, such as the fact that they can be isolated from the blood of the same patient, thus being immunologically compatible. Moreover, exosomes are distributed throughout the body, even being able to cross the intact blood‐brain barrier . In addition, in some cases, such as the exosomes released by mesenchymal stem cells (MSCs), they possess intrinsic therapeutic potential, akin to that of MSCs themselves, by being immunomodulatory and inducing tissue regeneration .…”

Section: Exosomes As Therapy For Diabetesmentioning

confidence: 99%

Exosomes and diabetes

Castaño

Novials

Párrizas

2019

Diabetes Metabolism Res

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Summary Diabetes is a group of metabolic diseases characterized by elevated blood glucose levels that drive the development of life‐threatening complications. Diabetes results from a situation of insufficient insulin action, either by deficient production of the hormone by the pancreas, or by the development of insulin resistance in peripheral tissues such as liver, muscle, or the adipose depots. Communication between organs is thus central to the maintenance of glucose homoeostasis. Recently, several studies are evidencing that small vesicles called exosomes released by, amongst other, the adipose tissue can regulate gene expression in other tissues, hence modulating interorgan crosstalk. Therefore, exosomes participate in the development of diabetes and its associated complications. Their study holds the potential of providing us with novel biomarkers for the early diagnosis and stratification of patients at risk of developing diabetes, hence allowing the timely implementation of more personalized therapies. On the other hand, the molecular dissection of the pathways initiated by exosomes under situations of metabolic stress could help to gain a deeper knowledge of the pathophysiology of diabetes and its associated metabolic diseases.

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“…García-Romero et al [123] showed that glioma-derived EVs such as exosomes and apoptotic bodies can be detected in peripheral blood and that they carry the relevant glioma-specific DNA mutations, such as AKT3, CDK4, CDKN2A, EGFR, ERBB2, IDH1/2, MDM2, PTEN and TP53. This study showed that exoDNA reflects crucial DNA alterations of the exosome releasing tumors.…”

Section: Application Of Exodna Analysis In Neuropathologymentioning

confidence: 99%

“…In the context of glioma diagnostics, IDH mutations are of special interest as they predominantly occur in diffuse and anaplastic glioma as well as in secondary glioblastoma. By analysis of exosomes, these characteristic IDH mutations may be detectable, both at the DNA and at the RNA levels [123,130]. The MGMT promoter methylation is of crucial importance for therapy planning in glioma patients.…”

Section: Application Of Exodna Analysis In Neuropathologymentioning

confidence: 99%

Emergence of exosomal DNA in molecular neuropathology

Kraus¹

2018

LaboratoriumsMedizin

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Background: Exosomes are small vesicles of sizes between 40 and 100 nm. They are actively segregated by numerous different cell types and they can be found in almost all body fluids. Thus, there is an emerging role of exosomes and exosomal deoxyribonucleic acid (exoDNA) in biomedical research, especially in molecular medicine. Exosomes are assembled and segregated actively and carry distinct surface markers for cellular communication. They are loaded with cargo such as DNA, ribonucleic acid (RNA) and proteins. As there are numerous different exosomal purification methods available, it is of essential need to select an appropriate technique to get reliable results. As neuropathology is faced with the challenge that brain tissue is not accessible in an easy fashion, exosomes represent an ideal tool for molecular neuro pathology. Thus, disease-specific molecular alterations will be detectable in a minimally invasive way for early disease diagnosis and surveillance. Summary: The analysis of exoDNA as biomarkers in neuropathology will enable early diagnosis, monitoring and relapse detection of brain tumors and neuropsychiatric disorders. Outlook: It is assumed that the significance of exosomes will increase in the upcoming years. There are powerful approaches in development using exosomes in molecularly targeted therapy to ultimately cure devastating brain diseases.

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DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

Cited by 206 publications

References 34 publications

Circulating biomarkers in patients with glioblastoma

Circulating biomarkers in patients with glioblastoma

Exosomes and diabetes

Emergence of exosomal DNA in molecular neuropathology

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