scholarly journals The functional curcumin liposomes induce apoptosis in C6 glioblastoma cells and C6 glioblastoma stem cells in vitro and in animals

2017 ◽  
Vol Volume 12 ◽  
pp. 1369-1384 ◽  
Author(s):  
Yahua Wang ◽  
Xue Ying ◽  
Haolun Xu ◽  
Helu Yan ◽  
Xia Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioblastoma Cells ◽  
Glioblastoma Stem Cells

scholarly journals CCR5-Mediated Signaling is Involved in Invasion of Glioblastoma Cells in Its Microenvironment

2020 ◽  
Vol 21 (12) ◽  
pp. 4199
Author(s):  
Metka Novak ◽  
Miha Koprivnikar Krajnc ◽  
Barbara Hrastar ◽  
Barbara Breznik ◽  
Bernarda Majc ◽  
...  
Keyword(s):  
Stem Cells ◽  
Low Grade ◽  
Glioblastoma Cells ◽  
Ccr5 Gene ◽  
Glioblastoma Stem Cells ◽  
Primary Glioblastoma ◽  
Tissue Sections ◽  
Stromal Microenvironment ◽  
Close Proximity

The chemokine CCL5/RANTES is a versatile inflammatory mediator, which interacts with the receptor CCR5, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which CCL5 expression correlates with shorter patient survival. Using immunohistochemistry, we identified CCL5 and CCR5 in a series of glioblastoma samples and cells, including glioblastoma stem cells. CCL5 and CCR5 gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on CCL5-induced CCR5 signaling and is strongly inhibited by the small molecule CCR5 antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release CCR5 ligands. In support of this model, we detected CCL5 and CCR5 in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found CCR5 expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves CCR5 and CCL5, contributing to glioblastoma invasion, suggesting the CCL5/CCR5 axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc.

scholarly journals OMRT-11. The effect of microenvironment on glioblastoma stem cells therapeutic resistance

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii9-ii9
Author(s):  
Tamara Lah Turnsek ◽  
Barbara Breznik ◽  
Bernarda Majc ◽  
Metka Novak ◽  
Andrej Porčnik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Combined Treatment ◽  
Cell Plasticity ◽  
Glioblastoma Stem Cells ◽  
Mesenchymal Transition ◽  
Non Invasive ◽  
Differential Gene

Abstract Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo. •1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782

scholarly journals Anti-vimentin, anti-TUFM, anti-NAP1L1 and anti-DPYSL2 nanobodies display cytotoxic effect and reduce glioblastoma cell migration

2020 ◽  
Vol 12 ◽  
pp. 175883592091530 ◽  
Author(s):  
Alja Zottel ◽  
Ivana Jovčevska ◽  
Neja Šamec ◽  
Jernej Mlakar ◽  
Jernej Šribar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Migration ◽  
Cell Lines ◽  
Water Soluble ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Mitochondrial Translation ◽  
Cytotoxic Effects ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Cell Lines

Background: Glioblastoma is a particularly common and very aggressive primary brain tumour. One of the main causes of therapy failure is the presence of glioblastoma stem cells that are resistant to chemotherapy and radiotherapy, and that have the potential to form new tumours. This study focuses on validation of eight novel antigens, TRIM28, nucleolin, vimentin, nucleosome assembly protein 1-like 1 (NAP1L1), mitochondrial translation elongation factor (EF-TU) (TUFM), dihydropyrimidinase-related protein 2 (DPYSL2), collapsin response mediator protein 1 (CRMP1) and Aly/REF export factor (ALYREF), as putative glioblastoma targets, using nanobodies. Methods: Expression of these eight antigens was analysed at the cellular level by qPCR, ELISA and immunocytochemistry, and in tissues by immunohistochemistry. The cytotoxic effects of the nanobodies were determined using AlamarBlue and water-soluble tetrazolium tests. Annexin V/propidium iodide tests were used to determine apoptotsis/necrosis of the cells in the presence of the nanobodies. Cell migration assays were performed to determine the effects of the nanobodies on cell migration. Results: NAP1L1 and CRMP1 were significantly overexpressed in glioblastoma stem cells in comparison with astrocytes and glioblastoma cell lines at the mRNA and protein levels. Vimentin, DPYSL2 and ALYREF were overexpressed in glioblastoma cell lines only at the protein level. The functional part of the study examined the cytotoxic effects of the nanobodies on glioblastoma cell lines. Four of the nanobodies were selected in terms of their specificity towards glioblastoma cells and protein overexpression: anti-vimentin (Nb79), anti-NAP1L1 (Nb179), anti-TUFM (Nb225) and anti-DPYSL2 (Nb314). In further experiments to optimise the nanobody treatment schemes, to increase their effects, and to determine their impact on migration of glioblastoma cells, the anti-TUFM nanobody showed large cytotoxic effects on glioblastoma stem cells, while the anti-vimentin, anti-NAP1L1 and anti-DPYSL2 nanobodies were indicated as agents to target mature glioblastoma cells. The anti-vimentin nanobody also had significant effects on migration of mature glioblastoma cells. Conclusion: Nb79 (anti-vimentin), Nb179 (anti-NAP1L1), Nb225 (anti-TUFM) and Nb314 (anti-DPYSL2) nanobodies are indicated for further examination for cell targeting. The anti-TUFM nanobody, Nb225, is particularly potent for inhibition of cell growth after long-term exposure of glioblastoma stem cells, with minor effects seen for astrocytes. The anti-vimentin nanobody represents an agent for inhibition of cell migration.

scholarly journals Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 579 ◽  
Author(s):  
Ivan Trus ◽  
Nathalie Berube ◽  
Peng Jiang ◽  
Janusz Rak ◽  
Volker Gerdts ◽  
...  
Keyword(s):  
Stem Cells ◽  
Zika Virus ◽  
Brain Cells ◽  
In Ovo ◽  
Glioblastoma Stem Cells ◽  
Oncolytic Therapy ◽  
Cpg Dinucleotide ◽  
Virus Interactions ◽  
Oncolytic Activity

We studied whether cytosine phosphate–guanine (CpG) recoding in a viral genome may provide oncolytic candidates with reduced infection kinetics in nonmalignant brain cells, but with high virulence in glioblastoma stem cells (GSCs). As a model, we used well-characterized CpG-recoded Zika virus vaccine candidates that previously showed genetic stability and safety in animal models. In vitro, one of the CpG-recoded Zika virus variants had reduced infection kinetics in nonmalignant brain cells but high infectivity and oncolytic activity in GSCs as represented by reduced cell proliferation. The recoded virus also efficiently replicated in GSC-derived tumors in ovo with a significant reduction of tumor growth. We also showed that some GSCs may be resistant to Zika virus oncolytic activity, emphasizing the need for personalized oncolytic therapy or a strategy to overcome resistance in GSCs. Collectively, we demonstrated the potential of the CpG recoding approach for oncolytic virus development that encourages further research towards a better understanding of host–tumor–CpG-recoded virus interactions.

Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Guoxin Zhang ◽  
Zhen Dong ◽  
Ryan C. Gimple ◽  
Arthur Wolin ◽  
Qiulian Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Phosphatase Activity ◽  
Expression Profiles ◽  
Tyrosine Phosphatase ◽  
Gene Expression Profiles ◽  
Therapeutic Index ◽  
Mitotic Catastrophe ◽  
Glioblastoma Stem Cells ◽  
Growth And Survival

Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.

scholarly journals Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells

2015 ◽  
Vol 11 (3) ◽  
pp. 331-346 ◽  
Author(s):  
Iolanda D’Alimonte ◽  
Eleonora Nargi ◽  
Mariachiara Zuccarini ◽  
Paola Lanuti ◽  
Patrizia Di Iorio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Antitumor Effect ◽  
In Vitro Growth ◽  
Receptor Ligands ◽  
Glioblastoma Stem Cells ◽  
Human Glioblastoma ◽  
Purine Receptor

scholarly journals PP54. NANO-ENCAPSULATED DISULFIRAM TARGETS GLIOBLASTOMA STEM CELLS IN VITRO AND IN VIVO BY MODULATION OF HYPOXIA-NF-KB PATHWAY

2017 ◽  
Vol 19 (suppl_1) ◽  
pp. i15-i15
Author(s):  
Dr Vinodh Kannappan ◽  
Dr Zhipeng Wang ◽  
Dr Peng Liu ◽  
Dr Sarah Brown ◽  
Ms Kate Butcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioblastoma Stem Cells
Sign in / Sign up

Export Citation Format

Share Document