Transcriptional Repression of Mad-Max Complex by Human Umbilical Cord Blood Stem Cells Downregulates Extracellular Signal-Regulated Kinase in Glioblastoma

Velpula, Kiran Kumar; Dasari, Venkata Ramesh; Tsung, Andrew J.; Dinh, Dzung H.; Rao, Jasti S.

doi:10.1089/scd.2011.0424

Cited by 12 publications

(7 citation statements)

References 41 publications

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“…Bar = 200 μm;. (E) GBM tissue specimen lysates for western blot analysis were prepared as described previously [ 30 ]. In vivo expression was studied by loading equal amounts of protein (40 μg) from tissue lysates onto 10-12% SDS-PAGE gels.…”

Section: Resultsmentioning

confidence: 99%

“…In exploring new therapeutic strategies to counter glioblastoma progression, our previous studies have shown that human umbilical cord blood stem cells (hUCBSC) provides a promising platform to treat glioblastoma [ 28 - 30 ]. We investigated the co-regulatory role of Sox2 and Twist1 in GSC and their combinatorial effect on stemness maintenance and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1

et al. 2011

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1

et al. 2011

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“…The GAPDH antibody was used to verify equal loading of proteins in all lanes. Approximately 300 µg of total protein cell lysates from both untreated and 1µM CR-42-24 GSC28 cells were incubated with 50 µL of protein G beads (Miltenyi Biotech) followed by 2 µg of TUBB4 antibody with end-to-end rotation overnight as described previously [20]. The obtained eluates were verified for the expression of GLUT1 and TUBB4.…”

Section: Methodsmentioning

confidence: 99%

GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

Guda

Labak

Omar

et al. 2019

Cancers

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Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor’s shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma’s and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1’s binding with fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 however, TUBB4 expression is unaltered upon fasentin treatment. Using human pluripotent stem cell antibody array, we demonstrate reduced levels of Oct3/4, Nanog, Sox2, Sox17, Snail and VEGFR2 (Vascular endothelial growth factor receptor 2) upon CR-42-24 treatment. Overall, our data confirm that silencing TUBB4 or GLUT1 reduce GSC tumorsphere formation, self-renewal and proliferation in vitro. These findings suggest GLUT1 and its binding partner TUBB4 as druggable targets that warrant further investigation in GBM.

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“…hUCBMSCs are also reported to decrease glioblastoma cell invasion and migration by increasing PTEN or Mad1 expression and downregulating PI3K/AKT, c-Myc/ERK or EGFR/c-Met activities [ 187 , 188 ]. Inhibition of Wnt signaling has been shown to decrease tumor growth and migration after treatment with hUCMSC- or hADMSC- CM in bile duct cancer and breast cancer, respectively [ 189 , 190 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

et al. 2021

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Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, and their easy access and isolation. Currently, there are more than 1200 registered MSC clinical trials globally. However, a lack of standardized methods to characterize cell safety, efficacy, and biodistribution dramatically hinders the progress of MSC utility in clinical practice. In this review, we summarize the current state of MSC-based cell therapy, focusing on the systemic safety and biodistribution of MSCs. MSC-associated risks of tumor initiation and promotion and the underlying mechanisms of these risks are discussed. In addition, MSC biodistribution methodology and the pharmacokinetics and pharmacodynamics of cell therapies are addressed. Better understanding of the systemic safety and biodistribution of MSCs will facilitate future clinical applications of precision medicine using stem cells.

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Transcriptional Repression of Mad-Max Complex by Human Umbilical Cord Blood Stem Cells Downregulates Extracellular Signal-Regulated Kinase in Glioblastoma

Cited by 12 publications

References 41 publications

Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1

Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist1

GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

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