Multidrug resistance in glioblastoma stem-like cells: Role of the hypoxic microenvironment and adenosine signaling

Uribe, Daniel; Torres, Ángelo; Rocha, José Dellis; Niechi, Ignacio; Oyarzún, Carlos; Sobrevía, Luis; Martin, R. H.; Quezada, Claudia

doi:10.1016/j.mam.2017.01.009

Cited by 111 publications

(99 citation statements)

References 134 publications

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“…The response rate to current chemotherapies for cancer depends on the availability of various chemotherapy regimens. However, multidrug resistance (MDR) still develops nearly in all patients with cancers and leads to chemotherapy failure [32,33]. We tested the ability of THTMP and TMZ on creating drug-resistant tumor cells.…”

Section: Resistance Variantsmentioning

confidence: 99%

Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

Doan

Musa

Murugesan

et al. 2020

Cells

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Cancer stem cells (CSCs), a small subpopulation of cells existing in the tumor microenvironment promoting cell proliferation and growth. Targeting the stemness of the CSC population would offer a vital therapeutic opportunity. 3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP), a small synthetic phenol compound, is proposed to play a significant role in controlling the CSC proliferation and survival. We assessed the potential therapeutic effects of THTMP on glioblastoma multiforme (GBM) and its underlying mechanism in various signaling pathways. To fully comprehend the effect of THTMP on the CSCs, CD133 + GBM stem cell (GSC) and CD133 -GBM Non-stem cancer cells (NSCC) population from LN229 and SNB19 cell lines was used. Cell cycle arrest, apoptosis assay and transcriptome analysis were performed for individual cell population. THTMP strongly inhibited NSCC and in a subtle way for GSC in a time-dependent manner and inhibit the resistance variants better than that of temozolomide (TMZ). THTMP arrest the CSC cell population at both G1/S and G2/M phase and induce ROS-mediated apoptosis. Gene expression profiling characterize THTMP as an inhibitor of the p53 signaling pathway causing DNA damage and cell cycle arrest in CSC population. We show that the THTMP majorly affects the EGFR and CSC signaling pathways. Specifically, modulation of key genes involved in Wnt, Notch and Hedgehog, revealed the significant role of THTMP in disrupting the CSCs' stemness and functions. Moreover, THTMP inhibited cell growth, proliferation and metastasis of multiple mesenchymal patient-tissue derived GBM-cell lines. THTMP arrests GBM stem cell cycle through the modulation of EGFR and CSC signaling pathways.

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Section: Resistance Variantsmentioning

confidence: 99%

Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

Doan

Musa

Murugesan

et al. 2020

Cells

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“…It is, therefore, possible to monitor TMZ failure by analyzing the molecular components of GB tumor-derived EVs [116]. Other EV surface proteins such as CD44 and CD133 [117] may serve as biomarkers for chemoresistant GB patients. It is because glioblastoma stem-like cells responsible for chemoresistance and tumor recurrence also express the same cell surface markers [118].…”

Section: Diagnostic/prognostic Potential Of Ev Biomarkersmentioning

confidence: 99%

The potential diagnostic and prognostic role of extracellular vesicles in glioma: current status and future perspectives

et al. 2019

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Lack of appropriate diagnostic/prognostic tools for glioblastoma (GB) is considered one of the major setbacks in the early diagnosis and treatment of this deadly brain tumor. The current gold standard for its diagnosis and staging still relies on invasive biopsy followed by histological examination as well as molecular profiling. Nevertheless, noninvasive approaches are being explored and one example is through the investigation of extracellular vesicles (EVs) in the biofluids of GB patients. EVs are known to carry molecular cargoes such as DNA, mRNA, miRNA, proteins and lipids in almost every type of body fluids. Thus, molecular signature of GB may be present in the EVs derived from these patients. This review focuses on the diagnostic/prognostic potential of EVs in GB, through presenting recent studies on (i) molecular components of EVs, (ii) links between EVs and GB tumor microenvironment, and (iii) clinical potential of EV biomarkers, together with the technical shortcomings researchers need to consider for future studies. ARTICLE HISTORYAccording to their origin and/or size, EVs can be classified into three subclasses, which are apoptotic bodies,

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“…CSC are often enriched at sites of chronic hypoxia leading to the activation of the HIF pathway [200,202] . Interestingly, HIF activation leads to the initiation of protective pathways, including WNT and NOTCH, and genes of the ATP-binding cassette (ABC) drug transporter family members, such as MDR1, MRP1 and ABCG2 which are responsible for the efflux of cytotoxic drugs from the cells [203][204][205][206][207][208] . Additional, HIFindependent mechanisms have been reported [209] .…”

Section: Dormant Cancer Cells Are Resistant To the Cytotoxic Effects mentioning

confidence: 99%

Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

Peyvandi¹,

Lan²,

Lorusso³

et al. 2019

JCMT

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Breast cancer remains the main cause of cancer-related mortality for women worldwide. Main cause of death is the development of therapy-resistant metastases. Relapses occur with a bimodal temporal distribution, with a first peak at 1-2 years after initial therapy and a second peak 2-3 years later. This discontinuous growth kinetics is consistent with the notion that disseminated cancer cells can remain dormant over a prolonged period of time before resuming growth. How cancer cells enter, sustain and exit dormancy, are unanswered questions with relevance to cancer biology, monitoring and therapy. Investigating mechanisms of breast cancer dormancy remains challenging, as in patients the condition is elusive and experimentally there are only a few models that recapitulate the clinical condition. Thus, developing new models to identify clinically relevant mechanisms and candidate therapeutic targets may open new avenues for novel therapies to induce and prolong dormancy. We have observed that cells surviving chemotherapy can enter a state of immunological dormancy. Using this model, we identified IRF-7/Interferon type I/IFNRA as signaling axis essential for this effect. Here we will review concepts and recent developments in cancer metastasis and dormancy with emphasis on breast cancer, and elaborate strategies to exploit them therapeutically.

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Multidrug resistance in glioblastoma stem-like cells: Role of the hypoxic microenvironment and adenosine signaling

Cited by 111 publications

References 134 publications

Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

Glioblastoma Multiforme Stem Cell Cycle Arrest by Alkylaminophenol through the Modulation of EGFR and CSC Signaling Pathways

The potential diagnostic and prognostic role of extracellular vesicles in glioma: current status and future perspectives

Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

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