Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587

Figueroa, Javier; Phillips, Lynette M.; Shahar, Tal; Hossain, Anwar; Gumin, Joy; Kim, Hoon; Bean, Andrew J.; Calin, George A.; Fueyo, Juan; Walters, Edgar T.; Kalluri, Raghu; Verhaak, Roeland; Lang, Frederick F.

doi:10.1158/0008-5472.can-16-2524

Cited by 183 publications

(159 citation statements)

References 41 publications

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“…EVs contain surface molecules such as HLA-DR, 47 we figured that the cellular interaction might be subject-specific and thus question the use of DCs from different human donors. It has however been shown several times that miRNAs can be functionally transferred to target cells [48][49][50][51][52][53] and that DC function is modulated by EVs. [54][55][56] Thus, it is intriguing to speculate that sEVs-associated epithelial…”

Section: Discussionmentioning

confidence: 99%

Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

Bartel

Grutta

Cilluffo

et al. 2019

Allergy

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Background miRNAs are master regulators of signaling pathways critically involved in asthma and are transferred between cells in extracellular vesicles (EV). We aimed to investigate whether the miRNA content of EV secreted by primary normal human bronchial epithelial cells (NHBE) is altered upon asthma development. Methods NHBE cells were cultured at air‐liquid interface and treated with interleukin (IL)‐13 to induce an asthma‐like phenotype. EV isolations by precipitation from basal culture medium or apical surface wash were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blot, and EV‐associated miRNAs were identified by a RT‐qPCR‐based profiling. Significant candidates were confirmed in EVs isolated by size‐exclusion chromatography from nasal lavages of children with mild‐to‐moderate (n = 8) or severe asthma (n = 9), and healthy controls (n = 9). Results NHBE cells secrete EVs to the apical and basal side. 47 miRNAs were expressed in EVs and 16 thereof were significantly altered in basal EV upon IL‐13 treatment. Expression of miRNAs could be confirmed in EVs from human nasal lavages. Of note, levels of miR‐92b, miR‐210, and miR‐34a significantly correlated with lung function parameters in children (FEV1FVC%pred and FEF25‐75%pred), thus lower sEV‐miRNA levels in nasal lavages associated with airway obstruction. Subsequent ingenuity pathway analysis predicted the miRNAs to regulate Th2 polarization and dendritic cell maturation. Conclusion Our data indicate that secretion of miRNAs in EVs from the airway epithelium, in particular miR‐34a, miR‐92b, and miR‐210, might be involved in the early development of a Th2 response in the airways and asthma.

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Section: Discussionmentioning

confidence: 99%

Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

Bartel

Grutta

Cilluffo

et al. 2019

Allergy

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“…491 Exosomes from glioma-associated MSCs increase the tumorigenicity of glioma stem-like cells by transferring miR-1587. 542 In addition, exosomes regenerate stem cell phenotypes by mediating the EMT or regulating stem cell-related signaling pathways, such as the Wnt pathway, Notch pathway, Hh pathway and other pathways, which convert cells into CSCs. 543 Exosomes have many advantages, such as low immunogenicity, biocompatibility, easy production, cytotoxicity, easy storage, high drug loading capacity, and long life and have become ideal drug carriers for cancer therapy.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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“…GICs were isolated from previously described glioma surgical specimens according to reported experimental methods (Figueroa et al 2017). Briefly, glioma specimens were dissociated and cultured in serum-free NSC medium, consisting of Dulbecco's Modification of Eagle's Medium/Ham's F12 with 2% B-27 (Invitrogen, Carlsbad, CA, USA), 20 ng/mL bFGF (Sigma-Aldrich, St. Louis, Missouri, USA), 20 ng/mL EGF (Sigma-Aldrich, St. Louis, Missouri, USA).…”

Section: Isolation Of Gicsmentioning

confidence: 99%

“…Although surgical techniques and adjuvant therapy have evolved over the decades, the treatment and prognosis of gliomas still face significant challenges (Tomiyama and Ichimura 2019). This undesirable result is due in part to the cell-autonomous functions of therapeutically resistant glioma-initiating cells (GICs) (Figueroa et al 2017). Therefore, an in-depth study of the molecular mechanisms associated with glioma is of great value in the development of potential glioma targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

Huo

Wang

Bai

et al. 2020

Mol Med

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Background: Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear.Methods: circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels.Results: circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes.Conclusion: circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

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Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587

Cited by 183 publications

References 41 publications

Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development

Targeting cancer stem cell pathways for cancer therapy

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

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