All-trans retinoic acid suppresses malignant characteristics of CD133-positive thyroid cancer stem cells and induces apoptosis

Mei, Dan; Lv, Bin; Chen, Bin; Xiao, Shan; Jiang, Jie; Xie, Yan; Jiang, Ling

doi:10.1371/journal.pone.0182835

Cited by 15 publications

(11 citation statements)

References 37 publications

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“…Prominin 1/CD133 significantly decreased in U87MG exposed to ATRA (10 −6 M, 1-fold, p = 0.003; 10 −4 M, 1.7-fold, p = 0.000024) in comparison to non-treated cells ( Figure 1 ). This data supports the role of ATRA in the inhibition of stem cell characteristics as seen with other cancer types, e.g., thyroid [ 24 ]. As glioblastoma has a sub-population of stem cells capable of self-renewal and radiotherapy resistance, the response of prominin-1/CD133 to ATRA in U87MG may potentially serve as a GBM cell line model for targeted differentiation strategies.…”

Section: Resultssupporting

confidence: 86%

All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma

et al. 2021

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Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.

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Section: Resultssupporting

confidence: 86%

All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma

et al. 2021

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“…In contrast, tretinoin, an analog of vitamin A, was first proven as a medication for acne [51], and has been used to treat APL since the 1990s [52]. Recent studies also reported its potential role on suppressing other cancers such as lung cancer [53] and thyroid cancer [54]. In this regard, our in vitro cell line results also revealed that tretinoin had synergetic effects with lower concentrations of sunitinib (Fig.…”

Section: Discussionmentioning

confidence: 56%

Targeting the TR4 nuclear receptor-mediated lncTASR/AXL signaling with tretinoin increases the sunitinib sensitivity to better suppress the RCC progression

Shi

Sun

et al. 2019

Oncogene

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Renal cell carcinoma (RCC) is one of the most lethal urological tumors. Using sunitinib to improve the survival has become the first-line therapy for metastatic RCC patients. However, the occurrence of sunitinib resistance in the clinical application has curtailed its efficacy. Here we found TR4 nuclear receptor might alter the sunitinib resistance to RCC via altering the TR4/lncTASR/AXL signaling. Mechanism dissection revealed that TR4 could modulate lncTASR (ENST00000600671.1) expression via transcriptional regulation, which might then increase AXL protein expression via enhancing the stability of AXL mRNA to increase the sunitinib resistance in RCC. Human clinical surveys also linked the expression of TR4, lncTASR, and AXL to the RCC survival, and results from multiple RCC cell lines revealed that targeting this newly identified TR4-mediated signaling with small molecules, including tretinoin, metformin, or TR4-shRNAs, all led to increase the sunitinib sensitivity to better suppress the RCC progression, and our preclinical study using the in vivo mouse model further proved tretinoin had a better synergistic effect to increase sunitinib sensitivity to suppress RCC progression. Future successful clinical trials may help in the development of a novel therapy to better suppress the RCC progression.

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“…The treatment of APL with ATRA leads to the dissociation of these repressor complexes and triggers the gene expression of the RARA-responsive genes [ 59 ]. The ATRA treatment was shown to sensitize different tumor types to the conventional treatment [ 56 , 58 , 60 , 61 ] and inhibit CSC populations [ 57 , 58 , 62 ]. In PCa, ATRA was shown to inhibit the proliferation of AR-negative cells by activating cyclin-dependent kinase 5 (Cdk5) and p27 expression [ 63 ].…”

Section: Aldh1a1mentioning

confidence: 99%

The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

Püschel

Dubrovska

Gorodetska

2021

Cancers

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Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation and drug resistant, leading to tumor relapse and metastases. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde dehydrogenase activity (ALDH) is widely accepted for prostate cancer (PCa) and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties, representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.

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All-trans retinoic acid suppresses malignant characteristics of CD133-positive thyroid cancer stem cells and induces apoptosis

Cited by 15 publications

References 37 publications

All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma

All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma

Targeting the TR4 nuclear receptor-mediated lncTASR/AXL signaling with tretinoin increases the sunitinib sensitivity to better suppress the RCC progression

The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

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