Chemoresistance, Cancer Stem Cells, and miRNA Influences: The Case for Neuroblastoma

Buhagiar, Alfred; Ayers, Duncan

doi:10.1155/2015/150634

Cited by 38 publications

(29 citation statements)

References 109 publications

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“…The existence of self-renewing multipotent tumor cells is considered a reservoir of malignant progenitors that are responsible for NB growth and lack of sensitivity to chemotherapeutics [35,36]. The above-described data on β3-AR role in the differentiation of NB cells, prompted us to investigate whether β3-AR modulation could alter stem cell features in human BE(2)C cells.…”

Section: β3-ar Blockade Reduces Stemness In Human Nb Be (2)c Cells Bymentioning

confidence: 99%

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation

et al. 2019

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Neuroblastoma (NB) is the most frequently observed among extracranial pediatric solid tumors. It displays an extreme clinical heterogeneity, in particular for the presentation at diagnosis and response to treatment, often depending on cancer cell differentiation/stemness. The frequent presence of elevated hematic and urinary levels of catecholamines in patients affected by NB suggests that the dissection of adrenergic system is crucial for a better understanding of this cancer. β3adrenoreceptor (β3-AR) is the last identified member of adrenergic receptors, involved in different tumor conditions, such as melanoma. Multiple studies have shown that the dysregulation of the bioactive lipid sphingosine 1-phosphate (S1P) metabolism and signaling is involved in many pathological diseases including cancer. However, whether S1P is crucial for NB progression and aggressiveness is still under investigation. Here we provide experimental evidence that β3-AR is expressed in NB, both human specimens and cell lines, where it is critically involved in the activation of proliferation and the regulation between stemness/differentiation, via its functional cross-talk with sphingosine kinase 2 (SK2)/S1P receptor 2 (S1P 2) axis. The specific antagonism of β3-AR by SR59230A inhibits NB growth and tumor progression, by switching from stemness to cell differentiation both in vivo and in vitro through the specific blockade of SK2/S1P 2 signaling.

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Section: β3-ar Blockade Reduces Stemness In Human Nb Be (2)c Cells Bymentioning

confidence: 99%

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation

et al. 2019

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“…ERCC4-and ERCC1-deficient cells have been reported to be 40 times more sensitive to cisplatin compared with the parental cells (5), supporting the role of these enzymes in the NER signaling pathway and cisplatin resistance. Increasing evidence suggests that microRNAs (miRNAs/miRs) influence the efficacy of chemotherapeutic drugs by regulating gene expression (6). miR-138 is abnormally expressed in various tumors, and has been associated with drug resistance in lung cancer (7)(8)(9), cervical cancer (10) and osteosarcoma (11) cell lines.…”

Section: Introductionmentioning

confidence: 99%

miR‑138‑5p modulates the expression of excision repair cross‑complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin

et al. 2018

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The microRNA (miR)-138-5p affects the chemotherapeutic sensitivity of several human cancer types. In the present study, the expression and regulatory mechanisms of miR-138-5p were investigated in the gastric cancer cell line SGC7901 and its cisplatin-resistant derivative SGC7901/DDP. Gene microarray and reverse transcription-quantitative polymerase chain reaction analyses revealed that miR-138-5p was expressed at significantly lower levels in SGC7901/DDP compared with SGC7901 cells. Using computational predictive algorithms, two proteins involved in the nuclear excision repair pathway were identified, excision repair cross-complementing (ERCC)1 and ERCC4, as putative miR-138-5p target genes. Western blot analysis confirmed that ERCC1 and ERCC4 expression levels were inversely proportional to miR-138-5p levels in SGC7901 and SGC7901/DDP cells. Furthermore, ERCC1 and ERCC4 were upregulated in SGC7901 cells expressing miR-138-5p-targeting short hairpin RNA and, conversely, downregulated in SGC7901/DDP cells overexpressing miR-138-5p, confirming that this miRNA regulates ERCC protein levels. Notably, miR-138-5p silencing enhanced the cisplatin resistance of SGC7901 cells, while miR-138-5p overexpression partially reversed the cisplatin resistance of SGC7901/DDP cells. Taken together, these data suggest that miR-138-5p regulates the sensitivity of gastric cancer cells to cisplatin, possibly by modulating expression of the DNA repair proteins ERCC1 and ERCC4.

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“…In neuroblastoma (NB) a common link between signaling cascades involved in tumorigenesis is hypoxia, and in hypoxic regions of NB, HIF1, and HIF2 have been shown to be expressed in cells with stem-like features (76). NB is the most common extracranial pediatric solid tumor, which often arises in infants and children up to 5 years (77). It originates from embryonic neural crest cells during early embryogenesis and mutated SCPs are likely also in these tumors the initiator cells (14).…”

Section: Csc Targeted Therapiesmentioning

confidence: 99%

Cancer Stem Cells in Pheochromocytoma and Paraganglioma

et al. 2020

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Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with high cardiovascular morbidity and variable risk of malignancy. The current therapy of choice is surgical resection. Nevertheless, PCCs/PGLs are associated with a lifelong risk of tumor persistence or recurrence. A high rate of germline or somatic mutations in numerous genes has been found in these tumors. For some, the tumorigenic processes are initiated during embryogenesis. Such tumors carry gene mutations leading to pseudohypoxic phenotypes and show more immature characteristics than other chromaffin cell tumors; they are also often multifocal or metastatic and occur at an early age, often during childhood. Cancer stem cells (CSCs) are cells with an inherent ability of self-renewal, de-differentiation, and capacity to initiate and maintain malignant tumor growth. Targeting CSCs to inhibit cancer progression has become an attractive anti-cancer therapeutic strategy. Despite progress for this strategy for solid tumors such as neuroblastoma, brain, breast, and colon cancers, no substantial advance has been made employing similar strategies in PCCs/PGLs. In the current review, we discuss findings related to the identification of normal chromaffin stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs in PCCs/PGLs. Additionally, we examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating especially recurrent and metastatic tumors.

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Chemoresistance, Cancer Stem Cells, and miRNA Influences: The Case for Neuroblastoma

Cited by 38 publications

References 109 publications

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation

miR‑138‑5p modulates the expression of excision repair cross‑complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin

Cancer Stem Cells in Pheochromocytoma and Paraganglioma

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