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.
MeSH terms
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AC133 Antigen
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Animals
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Antigens, CD / metabolism
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Biomarkers, Tumor
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Brain Neoplasms / metabolism
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Cadherins / metabolism
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Cord Blood Stem Cell Transplantation*
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Epithelial-Mesenchymal Transition
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Fetal Blood / cytology
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Fetal Blood / metabolism
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Glioblastoma / genetics
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Glycoproteins / metabolism
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Humans
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Mesenchymal Stem Cells / metabolism
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Mesenchymal Stem Cells / pathology
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Mice
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Mice, Nude
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Neoplasm Metastasis
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Nuclear Proteins / metabolism*
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Organic Cation Transport Proteins / metabolism*
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Peptides / metabolism
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Proto-Oncogene Proteins c-met / metabolism*
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RNA Interference
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RNA, Small Interfering
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SOXB1 Transcription Factors / metabolism*
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Transcriptional Activation
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Twist-Related Protein 1 / metabolism*
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Vimentin / metabolism
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Xenograft Model Antitumor Assays
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beta Catenin / metabolism
Substances
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AC133 Antigen
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Antigens, CD
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Biomarkers, Tumor
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Cadherins
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Glycoproteins
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Nuclear Proteins
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Organic Cation Transport Proteins
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PROM1 protein, human
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Peptides
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Prom1 protein, mouse
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RNA, Small Interfering
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SOX2 protein, human
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SOXB1 Transcription Factors
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TWIST1 protein, human
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Twist-Related Protein 1
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Vimentin
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beta Catenin
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solute carrier family 22 (organic cation transporter), member 3
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MET protein, human
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Proto-Oncogene Proteins c-met