The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

Tsutsumimoto, Takahiro; Williams, Paul J.; Yoneda, Toshiyuki

doi:10.1016/j.jbo.2014.10.002

Cited by 14 publications

(8 citation statements)

References 46 publications

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“…SH-SY5Y cells have low levels of migration and invasion, which are significantly greater when the level of endogenous TRPM2 is increased. To examine the effect of endogenous TRPM2 depletion on migration and invasion, SK-N-AS cells, which are an aggressive neuroblastoma cell line with high levels of migration and invasion 59 , were studied. TRPM2 depletion utilized CRISPR-Cas9 technology as described in " Materials and Methods ".…”

Section: Resultsmentioning

confidence: 99%

The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression

Bao

Festa

Hirschler-Laszkiewicz

et al. 2022

Sci Rep

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Transient receptor potential channel TRPM2 is highly expressed in many cancers and involved in regulation of key physiological processes including mitochondrial function, bioenergetics, and oxidative stress. In Stage 4 non-MYCN amplified neuroblastoma patients, high TRPM2 expression is associated with worse outcome. Here, neuroblastoma cells with high TRPM2 expression demonstrated increased migration and invasion capability. RNA sequencing, RT-qPCR, and Western blotting demonstrated that the mechanism involved significantly greater expression of integrins α1, αv, β1, and β5 in cells with high TRPM2 expression. Transcription factors HIF-1α, E2F1, and FOXM1, which bind promoter/enhancer regions of these integrins, were increased in cells with high TRPM2 expression. Subcellular fractionation confirmed high levels of α1, αv, and β1 membrane localization and co-immunoprecipitation confirmed the presence of α1β1, αvβ1, and αvβ5 complexes. Inhibitors of α1β1, αvβ1, and αvβ5 complexes significantly reduced migration and invasion in cells highly expressing TRPM2, confirming their functional role. Increased pAktSer473 and pERKThr202/Tyr204, which promote migration through mechanisms including integrin activation, were found in cells highly expressing TRPM2. TRPM2 promotes migration and invasion in neuroblastoma cells with high TRPM2 expression through modulation of integrins together with enhancing cell survival, negatively affecting patient outcome and providing rationale for TRPM2 inhibition in anti-neoplastic therapy.

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Section: Resultsmentioning

confidence: 99%

The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression

Bao

Festa

Hirschler-Laszkiewicz

et al. 2022

Sci Rep

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“…In parallel, TIMP-1, which negatively regulates MMP-9, was upregulated ( Figure 8 C). We investigated the effects on COX-2, a molecule that is associated with osteolytic bone metastasis in neuroblastoma [ 26 ], which promotes MMP expression. We observed that COX2 mRNA and protein expression were also downregulated ( Figure 8 A,B): in this case, a synergistic effect may be speculated.…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro

et al. 2018

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We conducted an in vitro study combining a rexinoid, 6-OH-11-O-hydroxyphenanthrene (IIF), and epigallocatechin-3-gallate (EGCG), which is the main catechin of green tea, on BE(2)-C, a neuroblastoma cell line representative of the high-risk group of patients. Neuroblastoma is the most common malignancy of childhood: high-risk patients, having N-MYC over-expression, undergo aggressive therapy and show high mortality or an increased risk of secondary malignancies. Retinoids are used in neuroblastoma therapy with incomplete success: the association of a second molecule might improve the efficacy. BE(2)-C cells were treated by EGCG and IIF, individually or in combination: cell viability, as evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was reduced, EGCG+IIF being the most effective treatment. Apoptosis occurred and the EGCG+IIF treatment decreased N-MYC protein expression and molecular markers of invasion (MMP-2, MMP-9 and COX-2). Zymography demonstrated nearly 50% inhibition of MMP activity. When BE(2)-C cells were grown in non-adherent conditions to enrich the tumor-initiating cell population, BE(2)-C-spheres were obtained. After 48 h and 72 h treatment, EGCG+IIF limited BE(2)-C-sphere formation and elicited cell death with a reduction of N-MYC expression. We concluded that the association of EGCG to IIF might be applied without toxic effects to overcome the incomplete success of retinoid treatments in neuroblastoma patients.

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“…Implanted in mice, SK-N-AS cells generate larger tumors with larger diameter tumor vessels compared to SK-N-DZ cells, possibly attributed to the increased VEGF protein expression in the SK-N-AS cell line (13). In addition, only SK-N-AS cells cause osteolytic bone metastases in nude mice (14), which is ascribed to high COX-2 and prostaglandin E2 (PGE2) expression in this cell line. Different MYCN ampli cation status in these cells (15,16), with SK-N-AS having only a single copy while SK-N-DZ carries ampli ed MYCN, led to their use in studies focused on MYC related treatments such as combination of uridine and dihydroorotate dehydrogenase (17).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression and Radiation Response of Two Distinct Neuroblastoma Cell Lines

Ritner¹,

Popović²,

Abouzeid³

et al. 2022

Preprint

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Background: External beam radiation is infrequently used for treatment of pediatric cancer such as neuroblastoma, typically reserved for palliative care in patients with aggressive metastatic disease who fail to respond to alternative treatments. Understanding effects of radiation on neuroblastoma cells could improve efficacy of this final means of therapy to decrease tumor burden and stabilize the disease. Methods: In this study, clonogenic assays were used to establish radiation responses for SK-N-AS and SK-N-DZ cell lines; cells were then irradiated at doses that cause 90% cell killing based on clonogenic assay and their RNA isolated and subjected to microarray analysis. In addition, cells were transfected with pre-miRNA constructs that led to overexpression of microRNAs miR-34a and miR-1228 in combination with radiation exposure to determine possible miRNA regulation of radiation response. Results: Statistically significant differences were detected for expression of several thousands of genes when the two cell lines were compared with each other. In contrast, radiation led only to minor gene expression differences of less than two-fold between irradiated and non-irradiated cultures in both cell lines. Overexpression of miR-34a and miR-1228 in either cell line did not change this outcome. Conclusion: Neuroblastoma cell lines SK-N-AS and SK-N-DZ are phenotypically diverse and gene expression differences between them are extensive. However, the regulation of gene expression in both of these cell lines is in a stable equilibrium even when exposed to stressors such as radiation.

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The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

Cited by 14 publications

References 46 publications

The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression

The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression

Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro

Gene Expression and Radiation Response of Two Distinct Neuroblastoma Cell Lines

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