{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:51Z","timestamp":1787027871305,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Understanding cancer etiology requires replicating the tumor microenvironment (TME), which significantly differs from standard in vitro cultures due to nutrient limitations, acidic pH, and oxidative stress. To address this, a microfluidic bioreactor (\u00b5BR) with an expanded culture surface was designed to optimize exosome enrichment and glioblastoma cell behavior. Using response surface methodology (RSM), key parameters\u2014including medium exchange volume and interval time\u2014were optimized, leading to about a six-fold increase in exosome concentration without artificial inducers. Characterization techniques (SEM, AFM, DLS, RT-qPCR, and ELISA) confirmed significant alterations in exosome profiles, cancer stemness, and epithelial-mesenchymal transition (EMT)-related markers. Notably, EMT was induced in the \u00b5BR system, with a six-fold increase in HIF-1\u03b1 protein despite normoxic conditions, suggesting activation of compensatory signaling pathways. Molecular analysis showed upregulation of SOX2, OCT4, and Notch1, with SOX2 protein reaching 28 ng\/mL, while it was undetectable in traditional culture. Notch1 concentration tripled in the \u00b5BR system, correlating with enhanced stemness and phenotypic heterogeneity. Immunofluorescent microscopy confirmed nuclear SOX2 accumulation and co-expression of SOX2 and HIF-1\u03b1 in dedifferentiated CSC-like cells, demonstrating tumor heterogeneity. These findings highlight the \u00b5BR\u2019s ability to enhance stemness and mimic glioblastoma\u2019s aggressive phenotype, establishing it as a valuable platform for tumor modeling and therapeutic development.<\/jats:p>","DOI":"10.3390\/cells14090676","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:38:06Z","timestamp":1746531486000},"page":"676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Optimization of In-Situ Exosome Enrichment Methodology On-a-Chip to Mimic Tumor Microenvironment Induces Cancer Stemness in Glioblastoma Tumor Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3571-8149","authenticated-orcid":false,"given":"Saleheh","family":"Saffar","sequence":"first","affiliation":[{"name":"Department of Biology, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-8890","authenticated-orcid":false,"given":"Ali","family":"Ghiaseddin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI 48824-1322, USA"},{"name":"Institute for Stem Cell Research and Regenerative Medicine, Tehran University of Medical Sciences, Tehran 1419733151, Iran"},{"name":"Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 1411713116, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4202-9931","authenticated-orcid":false,"given":"Shiva","family":"Irani","sequence":"additional","affiliation":[{"name":"Department of Biology, Science and Research Branch, Islamic Azad University, Tehran 1477893855, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Ali","family":"Hamidieh","sequence":"additional","affiliation":[{"name":"Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran 1419733151, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hicks, W.H., Bird, C.E., Traylor, J.I., Shi, D.D., El Ahmadieh, T.Y., Richardson, T.E., Mcbrayer, S.K., and Abdullah, K.G. (2021). Contemporary Mouse Models in Glioma Research. Cells, 10.","DOI":"10.3390\/cells10030712"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nbt.2858","article-title":"Development and Function of Human Innate Immune Cells in a Humanized Mouse Model","volume":"32","author":"Rongvaux","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ramzy, G.M., Koessler, T., Ducrey, E., McKee, T., Ris, F., Buchs, N., Rubbia-Brandt, L., Dietrich, P.Y., and Nowak-Sliwinska, P. (2020). Patient-Derived in Vitro Models for Drug Discovery in Colorectal Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12061423"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jin, J., Yoshimura, K., Sewastjanow-Silva, M., Song, S., and Ajani, J.A. (2023). Challenges and Prospects of Patient-Derived Xenografts for Cancer Research. Cancers, 15.","DOI":"10.3390\/cancers15174352"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1038\/s12276-024-01272-5","article-title":"Patient-Derived Tumor Organoids: A New Avenue for Preclinical Research and Precision Medicine in Oncology","volume":"56","author":"Thorel","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108094","DOI":"10.1016\/j.isci.2023.108094","article-title":"In Vitro Vascularized Immunocompetent Patient-Derived Model to Test Cancer Therapies","volume":"26","author":"Deforges","year":"2023","journal-title":"iScience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1039\/C9LC00550A","article-title":"Tumor-on-a-Chip for Integrating a 3D Tumor Microenvironment: Chemical and Mechanical Factors","volume":"20","author":"Wan","year":"2020","journal-title":"Lab Chip"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.trecan.2022.03.006","article-title":"Microfluidics Meets 3D Cancer Cell Migration","volume":"8","author":"Mehta","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.tibtech.2023.10.001","article-title":"Cancer-on-Chip Models for Metastasis: Importance of the Tumor Microenvironment","volume":"42","author":"Jouybar","year":"2024","journal-title":"Trends Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cauli, E., Polidoro, M.A., Marzorati, S., Bernardi, C., Rasponi, M., and Lleo, A. (2023). Cancer-on-Chip: A 3D Model for the Study of the Tumor Microenvironment. J. Biol. Eng., 17.","DOI":"10.1186\/s13036-023-00372-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117146","DOI":"10.1016\/j.ces.2021.117146","article-title":"Modeling Mass Transfer in Stirred Microbioreactors","volume":"248","author":"Farsani","year":"2022","journal-title":"Chem. Eng. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xie, Y., Chindam, C., Nama, N., Yang, S., Lu, M., Zhao, Y., Mai, J.D., Costanzo, F., and Huang, T.J. (2015). Exploring Bubble Oscillation and Mass Transfer Enhancement in Acoustic-Assisted Liquid-Liquid Extraction with a Microfluidic Device. Sci. Rep., 5.","DOI":"10.1038\/srep12572"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Leach, T., Gandhi, U., Reeves, K.D., Stumpf, K., Okuda, K., Marini, F.C., Walker, S.J., Boucher, R., Chan, J., and Cox, L.A. (2023). Development of a Novel Air\u2014Liquid Interface Airway Tissue Equivalent Model for in Vitro Respiratory Modeling Studies. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-36863-1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hong, H., Song, J.M., and Yeom, E. (2022). Quantitative Study for Control of Air\u2013Liquid Segmented Flow in a 3D-Printed Chip Using a Vacuum-Driven System. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-13165-6"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12964-020-0530-4","article-title":"Tumor Microenvironment Complexity and Therapeutic Implications at a Glance","volume":"4","author":"Baghban","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.addr.2021.04.018","article-title":"Translating Complexity and Heterogeneity of Pancreatic Tumor: 3D in Vitro to in Vivo Models","volume":"174","author":"Heinrich","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The Tumor Microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bule, P., Aguiar, S.I., Aires-da-silva, F., Nunes, J., Dias, R., and Baranowska-bosiacka, I. (2021). Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189804"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cavallari, C., Camussi, G., and Brizzi, M.F. (2020). Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186768"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41568-018-0006-7","article-title":"A History of Exploring Cancer in Context","volume":"18","author":"Maman","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12935-020-01719-5","article-title":"The Role of Hypoxia in the Tumor Microenvironment and Development of Cancer Stem Cell: A Novel Approach to Developing Treatment","volume":"21","author":"Najafgholian","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1136\/jcp.s3-11.1.105","article-title":"Hypoxia and Tumours","volume":"30","author":"Thomlinson","year":"1977","journal-title":"J. Clin. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Macharia, L.W., Wanjiru, C.M., Mureithi, M.W., Pereira, C.M., Ferrer, V.P., and Moura-Neto, V. (2019). MicroRNAs, Hypoxia and the Stem-like State as Contributors to Cancer Aggressiveness. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00125"},{"key":"ref_26","first-page":"2334","article-title":"Conditioned Medium Mimicking the Tumor Microenvironment Augments Chemotherapeutic Resistance via Ataxia-Telangiectasia Mutated and Nuclear Factor-\u039aB Pathways in Gastric Cancer Cells","volume":"40","author":"Zhuang","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Basmaeil, Y., Al Subayyil, A., Abumaree, M., and Khatlani, T. (2021). Conditions Mimicking the Cancer Microenvironment Modulate the Functional Outcome of Human Chorionic Villus Mesenchymal Stem\/Stromal Cells in Vitro. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.650125"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xie, H., Appelt, J.W., and Jenkins, R.W. (2021). Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology. Cancers, 13.","DOI":"10.3390\/cancers13236052"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Devarasetty, M., Dominijanni, A., Herberg, S., Shelkey, E., Skardal, A., and Soker, S. (2020). Simulating the Human Colorectal Cancer Microenvironment in 3D Tumor-Stroma Co-Cultures in Vitro and in Vivo. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-66785-1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.trecan.2021.06.009","article-title":"Tumour Microenvironment 3D-Modelling: Simplicity to Complexity and Back Again","volume":"7","author":"Carter","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12323","DOI":"10.1002\/jev2.12323","article-title":"Convection and Extracellular Matrix Binding Control Interstitial Transport of Extracellular Vesicles","volume":"12","author":"Sariano","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12280","DOI":"10.1002\/jev2.12280","article-title":"A Human Kidney and Liver Organoid-Based Multi-Organ-on-a-Chip Model to Study the Therapeutic Effects and Biodistribution of Mesenchymal Stromal Cell-Derived Extracellular Vesicles","volume":"11","author":"Nguyen","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1039\/C3LC50993A","article-title":"Microfluidic Fabrication of Cell-Derived Nanovesicles as Endogenous RNA Carriers","volume":"14","author":"Jo","year":"2014","journal-title":"Lab Chip"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1039\/C8LC00246K","article-title":"Microfluidic Engineering of Exosomes: Editing Cellular Messages for Precision Therapeutics","volume":"18","author":"Zhu","year":"2018","journal-title":"Lab Chip"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.tcb.2017.06.003","article-title":"Metabolic Interactions in the Tumor Microenvironment","volume":"27","author":"Lyssiotis","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Vander Understanding the Warburg Effect","volume":"324","author":"Heiden","year":"2009","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(83)90040-5","article-title":"Fate of the Transferrin Receptor during Maturation of Sheep Reticulocytes in Vitro: Selective Externalization of the Receptor","volume":"33","author":"Pan","year":"1983","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9412","DOI":"10.1016\/S0021-9258(18)48095-7","article-title":"Vesicle Formation during Reticulocyte Maturation","volume":"262","author":"Johnstone","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by Extracellular Vesicles: Where We Are and Where We Need to Go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/nar\/gkr828","article-title":"ExoCarta 2012: Database of Exosomal Proteins, RNA and Lipids","volume":"40","author":"Mathivanan","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Scott, S.M., and Ali, Z. (2021). Fabrication Methods for Microfluidic Devices: An Overview. Micromachines, 12.","DOI":"10.3390\/mi12030319"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2100106","DOI":"10.1002\/adtp.202100106","article-title":"A 3D-Bioprinted Vascularized Glioblastoma-on-a-Chip for Studying the Impact of Simulated Microgravity as a Novel Pre-Clinical Approach in Brain Tumor Therapy","volume":"4","author":"Silvani","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1582398","DOI":"10.1080\/23311932.2019.1582398","article-title":"Determination of Cell Viability Using Acridine Orange\/Propidium Iodide Dual-Spectrofluorometry Assay","volume":"5","author":"Hussain","year":"2019","journal-title":"Cogent Food Agric."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4161\/cbt.5.1.2236","article-title":"Reversal of MDR1\/P-Glycoprotein-Mediated Multidrug Resistance by Vector-Based RNA Interference in Vitro and in Vivo","volume":"5","author":"Shi","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41405-023-00135-x","article-title":"Delivery of MicroRNA-302a-3p by APTES Modified Hydroxyapatite Nanoparticles to Promote Osteogenic Differentiation in Vitro","volume":"9","author":"Limlawan","year":"2023","journal-title":"BDJ Open"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6661","DOI":"10.1039\/D0NR09178B","article-title":"Structural and Mechanical Characteristics of Exosomes from Osteosarcoma Cells Explored","volume":"13","author":"Yurtsever","year":"2021","journal-title":"Nanoscale"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Passos Gibson, V., Tahiri, H., Yang, C., Phan, Q.T., Banquy, X., and Hardy, P. (2023). Hyaluronan Decorated Layer-by-Layer Assembled Lipid Nanoparticles for MiR-181a Delivery in Glioblastoma Treatment. Biomaterials, 302.","DOI":"10.1016\/j.biomaterials.2023.122341"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Shiri, F., Feng, H., Petersen, K.E., Sant, H., Bardi, G.T., Schroeder, L.A., Merchant, M.L., Gale, B.K., and Hood, J.L. (2022). Separation of U87 Glioblastoma Cell-Derived Small and Medium Extracellular Vesicles Using Elasto-Inertial Flow Focusing (a Spiral Channel). Sci. Rep., 12.","DOI":"10.1038\/s41598-022-10129-8"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0014-4827(83)90185-4","article-title":"Denaturation of RNA and DNA in Situ Induced by Acridine Orange","volume":"148","author":"Darzynkiewicz","year":"1983","journal-title":"Exp. Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7822","DOI":"10.1002\/cam4.2667","article-title":"Hypoxia-Induced HIF-1\u03b1 and ZEB1 Are Critical for the Malignant Transformation of Ameloblastoma via TGF-\u03b2-Dependent EMT","volume":"8","author":"Yoshimoto","year":"2019","journal-title":"Cancer Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11882","DOI":"10.18632\/oncotarget.3592","article-title":"Activation of Hypoxia Signaling Induces Phenotypic Transformation of Glioma Cells: Implications for Bevacizumab Antiangiogenic Therapy","volume":"6","author":"Xu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The Somatic Genomic Landscape of Glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S1535-6108(03)00304-0","article-title":"Downregulation of Caveolin-1 Function by EGF Leads to the Loss of E-Cadherin, Increased Transcriptional Activity of \u03b2-Catenin, and Enhanced Tumor Cell Invasion","volume":"4","author":"Lu","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1152\/ajpcell.00478.2005","article-title":"Molecular Pathways Regulating EGF-Induced Epithelio-Mesenchymal Transition in Human Ovarian Surface Epithelium","volume":"290","author":"Ahmed","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12964-023-01207-z","article-title":"NF-\u039aB Signaling in Neoplastic Transition from Epithelial to Mesenchymal Phenotype","volume":"21","author":"Oh","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_57","first-page":"3810","article-title":"Hypoxia Promotes Fibrogenesis in Vivo via HIF-1 Stimulation of Epithelial-to-Mesenchymal Transition","volume":"117","author":"Higgins","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"714","DOI":"10.4161\/cbt.11.8.15274","article-title":"EMT: A New Vision of Hypoxia Promoting Cancer Progression","volume":"11","author":"Jiang","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.ajpath.2012.01.040","article-title":"The Tumor Microenvironment Strongly Impacts Master Transcriptional Regulators and Gene Expression Class of Glioblastoma","volume":"180","author":"Cooper","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/7651_2021_371","article-title":"Cancer Stem Cell Initiation by Tumor-Derived Extracellular Vesicles","volume":"Volume 2549","author":"Afify","year":"2022","journal-title":"Methods in Molecular Biology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s10571-019-00771-8","article-title":"Glioblastoma Stem Cell-Derived Exosomes Enhance Stemness and Tumorigenicity of Glioma Cells by Transferring Notch1 Protein","volume":"40","author":"Sun","year":"2020","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S1097-2765(01)00260-X","article-title":"The Two-Handed E Box Binding Zinc Finger Protein SIP1 Downregulates E-Cadherin and Induces Invasion","volume":"7","author":"Comijn","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.canlet.2012.05.024","article-title":"Activation of Canonical WNT\/\u03b2-Catenin Signaling Enhances in Vitro Motility of Glioblastoma Cells by Activation of ZEB1 and Other Activators of Epithelial-to-Mesenchymal Transition","volume":"325","author":"Kahlert","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1172\/JCI200421358","article-title":"NF-\u039aB Is Essential for Epithelial-Mesenchymal Transition and Metastasis in a Model of Breast Cancer Progression","volume":"114","author":"Huber","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1443-14","DOI":"10.1038\/cddis.2014.395","article-title":"TGF-\u03b2 Is an Inducer of ZEB1-Dependent Mesenchymal Transdifferentiation in Glioblastoma That Is Associated with Tumor Invasion","volume":"5","author":"Joseph","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wang, H., Wang, H.S., Zhou, B.H., Li, C.L., Zhang, F., Wang, X.F., Zhang, G., Bu, X.Z., Cai, S.H., and Du, J. (2013). Epithelial-Mesenchymal Transition (EMT) Induced by TNF-\u03b1 Requires AKT\/GSK-3\u03b2-Mediated Stabilization of Snail in Colorectal Cancer. 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