Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype

Yu, Tianfu; Wang, Xiefeng; Zhi, Tongle; Zhang, Junxia; Wang, Yingyi; Nie, Er; Zhao, Fengqi; You, Yongping; Liu, Ning

doi:10.1016/j.canlet.2018.06.041

Cited by 77 publications

(63 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transfer of APNG and MGMT mRNAs, could generate these enzymes in the recipient cells and help repair and reverse the damage to DNA caused by TMZ (19). Interestingly, EVs released by tumor associated astrocytes were also shown to contain MGMT mRNA which induces TMZ resistant phenotype in sensitive glioma cells (97). High levels of miR-1238 were detected in EVs isolated from TMZ resistant cells as well as plasma of GBM patients.…”

Section: Evs Play a Role In Acquiring Drug Resistancementioning

confidence: 99%

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

et al. 2020

View full text Add to dashboard Cite

Glioblastomas (GBM) are highly aggressive primary brain tumors. Complex and dynamic tumor microenvironment (TME) plays a crucial role in the sustained growth, proliferation, and invasion of GBM. Several means of intercellular communication have been documented between glioma cells and the TME, including growth factors, cytokines, chemokines as well as extracellular vesicles (EVs). EVs carry functional genomic and proteomic cargo from their parental cells and deliver that information to surrounding and distant recipient cells to modulate their behavior. EVs are emerging as crucial mediators of establishment and maintenance of the tumor by modulating the TME into a tumor promoting system. Herein we review recent literature in the context of GBM TME and the means by which EVs modulate tumor proliferation, reprogram metabolic activity, induce angiogenesis, escape immune surveillance, acquire drug resistance and undergo invasion. Understanding the multifaceted roles of EVs in the niche of GBM TME will provide invaluable insights into understanding the biology of GBM and provide functional insights into the dynamic EV-mediated intercellular communication during gliomagenesis, creating new opportunities for GBM diagnostics and therapeutics.

show abstract

Section: Evs Play a Role In Acquiring Drug Resistancementioning

confidence: 99%

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Specifically, EVs derived from cancer-associated fibroblasts [115][116][117][118] , cancer-associated adipocytes [118] , and tumor-associated macrophages [119,120] in the tumor microenvironment have been shown to impart drug resistance in sensitive cells via the transfer of functional cargo. EVs derived from GBM associated macrophages and GBM associated astrocytes were also implicated in the development of TMZ resistance and radioresistance [109,121] .…”

Section: Evs Derived From Cells Of the Tumor Microenvironmentmentioning

confidence: 99%

The role of extracellular vesicles in acquisition of resistance to therapy in glioblastomas

Yekula¹,

Taylor²,

Beecroft³

et al. 2020

CDR

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking, followed by radiation therapy with concurrent and adjuvant temozolomide treatment. The natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after therapy. Several mechanisms including inter- and intratumoral heterogeneity, the evolution of therapy-resistant clonal subpopulations, reacquisition of stemness in glioblastoma stem cells, multiple drug efflux mechanisms, the tumor-promoting microenvironment, metabolic adaptations, and enhanced repair of drug-induced DNA damage have been implicated in therapy failure. Extracellular vesicles (EVs) have emerged as crucial mediators in the maintenance and establishment of GBM. Multiple seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug resistance. Mechanisms include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based therapies. In this review, we discuss the various mechanisms of therapy resistance in GBM, highlighting the emerging role of EV-orchestrated drug resistance. Understanding the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease.

show abstract

“…These exosomes, as one would expect, differ from exosomes secreted by normal glial cells in their cargo content. Exosomes derived from glioma cells have been reported to be enriched in oncogenic proteins (EGFRvIII), angiogenic factors, and coding as well as noncoding RNA species . Because exosomes are mainly involved in intercellular signaling, glioma cell‐derived exosomes essentially facilitate the horizontal propagation of oncogenic species between cancer cells, thereby creating a positive feedback loop, or between cancer cells and the neighboring stromal cells.…”

Section: Exosomes Control Glioma Progressionmentioning

confidence: 99%

“…Although this combinatorial approach has achieved an increase in the progression‐free survival period of patients, the overall survival largely remains unaffected. This has been largely ascribed to the gain of resistance by the surviving tumor cells against TMZ through the enhanced expression of the O‐6‐methylguanine DNA methyltransferase (MGMT) . In a modification of the above method, the additional use of supplementary drugs such as the new MGMT inhibitors has been tested in preclinical trials; however, these inhibitors run the great risk of inactivating DNA repair pathways in healthy cells.…”

Section: What Is Wrong With Conventional Glioma Therapy?mentioning

confidence: 99%

Extracellular Vesicles in Glioma: From Diagnosis to Therapy

Basu

Ghosh

2019

BioEssays

View full text Add to dashboard Cite

Increasing evidence indicates that extracellular vesicles (EVs) secreted from tumor cells play a key role in the overall progression of the disease state. EVs such as exosomes are secreted by a wide variety of cells and transport a varied population of proteins, lipids, DNA, and RNA species within the body. Gliomas constitute a significant proportion of all primary brain tumors and majority of brain malignancies. Glioblastoma multiforme (GBM) represents grade IV glioma and is associated with very poor prognosis despite the cumulative advances in diagnostic procedures and treatment strategies. Here, the authors describe the progress in understanding the role of EVs, especially exosomes, in overall glioma progression, and how new research is unraveling the utilities of exosomes in glioma diagnostics and development of next-generation therapeutic systems. Finally, based on an understanding of the latest scientific literature, a model for the possible working of therapeutic exosomes in glioma treatment is proposed.

show abstract

Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype

Cited by 77 publications

References 35 publications

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

The role of extracellular vesicles in acquisition of resistance to therapy in glioblastomas

Extracellular Vesicles in Glioma: From Diagnosis to Therapy

Contact Info

Product

Resources

About