title: Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1.
abstract: The dynamic nature of cancer stem cells that underlie metastasis or their ability to switch between different cellular identities, as in EMT and MET, has profound implications for cancer therapy. The functional relationship between molecules involved in cancer cell stemness and metastasis is not clear. In this regard, our studies on hGBM tissue grade IV specimens showed significant expression of Twist1 and Sox2, known mesenchymal and stemness related markers, respectively, indicating their association with glial tumor genesis and metastasis. The glioma stem cells obtained from CD133+ cells demonstrated increased expression of Twist1 and Sox2 accompanied by significant increase in the mesenchymal markers such as N-cadherin, vimentin and β-catenin. Our studies on glioma stem cells treatment with human umbilical cord blood derived- mesenchymal stem cells, showed down regulation of Twist1 and Sox2 proteins, apart from other mesenchymal stem cell markers. Based on the in vitro experiments and in vivo intracranial xenograft mouse model studies, we elucidated the potential therapeutic role of hUCBSC in suppressing glioma cancer stemness by the induction of MET.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Velpula
authors.forename: Venkata Ramesh
authors.initials: VR
authors.lastname: Dasari
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tsung
authors.forename: Dzung H
authors.initials: DH
authors.lastname: Dinh
authors.forename: Jasti S
authors.initials: JS
authors.lastname: Rao
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D036101:Cord Blood Stem Cell Transplantation; D058750:Epithelial-Mesenchymal Transition; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism; D000099254:Organic Cation Transporter 3
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D006023:Glycoproteins; D009687:Nuclear Proteins; D027701:Organic Cation Transport Proteins; D010455:Peptides; D019859:Proto-Oncogene Proteins c-met; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin; D000099254:Organic Cation Transporter 3; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse; C527782:SOX2 protein, human; C103173:TWIST1 protein, human; C491743:MET protein, human