Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Ma, Chenkai; Nguyen, Huy; Jones, Jordan; Stylli, Stanley S.; Whitehead, Clarissa A.; Paradiso, Lucy; Luwor, Rodney B; Areeb, Zammam; Hanssen, Eric; Cho, Hyun Jung; Putz, Ulrich; Kaye, Andrew H.; Morokoff, Andrew

doi:10.3390/ijms23052770

Cited by 26 publications

(27 citation statements)

References 64 publications

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“…These receptor cells survived radiation exposure and could efficiently form colonies, significantly enhancing cell migration and invasion. Mechanistic findings indicated that GSC-EV and its specifically wrapped miRNAs might induce phenotypic changes in the recipient cells by activating the PTEN/Akt pathway [ 93 ]. In addition, it was also shown that recombinant SEVs (R-EXO) from homologous glioma cells could carry TMZ and dihydrotanshinone (DHT), can reverse drug resistance, and enhance focal targeted drug delivery, defined as R-EXO-TMZ/DHT (R-EXO-T/D).…”

Section: The Roles Of Texs In Chemoresistancementioning

confidence: 99%

“…Exosome-derived circZNF652 is significantly up-day expressed in glioma cells and can be taken up by other glioma cells. The entry of circ-0001445 into glioma cells promotes glioma migration and invasion by regulating the miR-486-5p/SERPINE1 signaling axis and the epithelial–mesenchymal transition process [ 93 ].…”

Section: The Roles Of Texs In Invasion and Metastasismentioning

confidence: 99%

“…The entry of circ-0001445 into glioma cells promotes glioma migration and invasion by regulating the miR-486-5p/SERPINE1 signaling axis and the epithelial–mesenchymal transition process [ 93 ].…”

Section: The Roles Of Texs In Invasion and Metastasismentioning

confidence: 99%

“…Glioma cells Target CADM1/STAT3 signal Promote cell proliferation and metastasis [114] Glioma cells lnc-ATB astrocytes Target Ago2/miR-204-3p signal Induce astrocytes [115] Glioma cells miR-375 Glioma cells Target CTGF-EGFR signal Inhibit cell proliferation and invasion [116] Hypoxia glioma cells miR-1246 and miR-10b-5p Normoxia glioma cells Target FRK and TFAP2A Promote cell migration and invasion [117] Glioma cells circ-0001445 Glioma cells Target miR-127-5p/SNX5 Promote cell migration and invasion [118] Glioma cells circZNF652 Glioma cells Target miR-486-5p/SERPINE1 Promote cell migration, invasion and EMT [93] Fig. 6 The features of tumor angiogenesis.…”

Section: Glioma Cells Mir-148amentioning

confidence: 99%

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Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

2022

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Small extracellular vesicles (SEVs) are extracellular vesicles containing DNA, RNA, and proteins and are involved in intercellular communication and function, playing an essential role in the growth and metastasis of tumors. SEVs are present in various body fluids and can be isolated and extracted from blood, urine, and cerebrospinal fluid. Under both physiological and pathological conditions, SEVs can be released by some cells, such as immune, stem, and tumor cells, in a cytosolic manner. SEVs secreted by tumor cells are called tumor-derived exosomes (TEXs) because of their origin in the corresponding parent cells. Glioma is the most common intracranial tumor, accounting for approximately half of the primary intracranial tumors, and is characterized by insidious onset, high morbidity, and high mortality rate. Complete removal of tumor tissues by surgery is difficult. Chemotherapy can improve the survival quality of patients to a certain extent; however, gliomas are prone to chemoresistance, which seriously affects the prognosis of patients. In recent years, TEXs have played a vital role in the occurrence, development, associated immune response, chemotherapy resistance, radiation therapy resistance, and metastasis of glioma. This article reviews the role of TEXs in glioma progression, drug resistance, and clinical diagnosis.

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Section: The Roles Of Texs In Chemoresistancementioning

confidence: 99%

Section: The Roles Of Texs In Invasion and Metastasismentioning

confidence: 99%

Section: The Roles Of Texs In Invasion and Metastasismentioning

confidence: 99%

Section: Glioma Cells Mir-148amentioning

confidence: 99%

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Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

2022

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“…Intercellular communication between GBM and the tumor microenvironment is achieved via direct exchange through ion channels, transporters, gap junctions, and extracellular vesicles, as well as secretion of cytokines, chemokines, and neurotransmitters [ 40 ]. Extracellular vesicles can transport microRNA and proteins that remodel the microenvironment to promote tumor aggressiveness, stimulate angiogenesis, and promote resistance to therapy, including chemotherapeutics and radiation [ 46 ]. Moreover, specific GSC subtypes localizing to different niches are shown to produce distinct extracellular vesicles that contribute to intratumoral heterogeneity [ 47 ].…”

Section: Interactions With Tumor Microenvironmentmentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

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Glioma stem cell‐derived exosomes induce the transformation of astrocytes via the miR‐3065‐5p/DLG2 signaling axis

Li,

Zhu,

Liu

et al. 2024

Glia

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Tumor‐associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC‐derived exosomes (GSC‐EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC‐EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA‐related markers (TGF‐β, CD44, and tenascin‐C) were observed in the TAAs. Furthermore, GSC‐derived exosomal miR‐3065‐5p could be delivered to NHAs, and miR‐3065‐5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR‐3065‐5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA‐related markers. In addition, both GSC‐EXO‐induced and miR‐3065‐5p‐overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR‐3065‐5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC‐EXOs induce the transformation of NHAs into TAAs via the miR‐3065‐5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in‐depth mechanistic studies are still needed.

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Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Cited by 26 publications

References 64 publications

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Glioma stem cell‐derived exosomes induce the transformation of astrocytes via the miR‐3065‐5p/DLG2 signaling axis

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