Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria

Samardžija, Gordana; Stevović, Tamara Kravić; Djuričić, Slaviša; Djokic, Dragomir; Djurisic, M; Ćirić, Darko; Martinović, Tamara; Bumbaširević, Vladimir; Vujić, Dragana

doi:10.1080/01913123.2016.1187689

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…Autophagy serves an important role in the proliferation of colorectal cancer cells ( 3 ), and a number of studies have suggested that autophagy prevents metabolites from damaging cells and genomes ( 4 , 5 ). Conversely, other studies have suggested that autophagy contributes to the supply of nutrients and reused metabolites to tumor cells, therefore promoting their survival and proliferation ( 6 , 7 ). Although autophagy has been demonstrated to affect the proliferation of tumor cells, the regulatory mechanism underlying autophagy in colon cancer cells has not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Activation of the SphK1/ERK/p‑ERK pathway promotes autophagy in colon cancer cells

Zhang

Liu

et al. 2018

Oncol Lett

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Sphingosine kinase 1 (SphK1) is a master kinase that catalyzes the synthesis of sphingosine 1 phosphate and participates in the regulation of cell proliferation and autophagy. The present study aimed to assess the effects of the activation of the SphK1/extracellular signal-regulated kinase (ERK)/phosphorylated (p-)ERK pathway in the regulation of autophagy in colon cancer (HT-29) cells. Inverted fluorescence microscopy was used to detect the expression of green fluorescent protein (GFP) in the SphK1-overexpressing HT-29 cells [SphK1(+)-HT-29] and the negative control HT-29 cells (NC-HT-29). Western blotting was used to detect the protein expression levels of SphK1, ERK1/2, p-ERK1/2, as well as those of the autophagy-associated markers LC3A, ATG5, and ULK1. Protein localization and expression of the LC3A antibody were detected by immunofluorescence. The results demonstrated that GFP was similarly expressed in SphK1(+)-HT-29 and NC-HT-29 cells. However, significantly increased SphK1 mRNA and protein expression levels were detected in SphK1(+)-HT-29 cells compared with in NC-HT-29 cells, which resulted in upregulated ERK/p-ERK. Furthermore, the protein expression levels of the three autophagy-associated markers increased. LC3A protein was localized in the cytoplasm of SphK1(+)-HT-29 cells, indicating autophagy. In summary, the findings of the present study suggested that activation of the SphK1/ERK/p-ERK pathway promotes autophagy in colon cancer HT-29 cells.

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Section: Introductionmentioning

confidence: 99%

Activation of the SphK1/ERK/p‑ERK pathway promotes autophagy in colon cancer cells

Zhang

Liu

et al. 2018

Oncol Lett

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“…The increase in the number of NSGs in tumours with an unfavorable prognosis, could be explained either by an increase in the rate of their biogenesis or a disorder that effects the regulatory mechanisms of autophagy in these cells (11). Disruption in autophagy, the catabolic process in which a cell digests and eliminates its own macromolecules and organelles, could link the relatively larger number of NSGs to a poor prognosis (12).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural morphometry of neurosecretory granules in the neuroblastomas of paediatric patients

Jovanović¹,

Kravić-Stevović²

2018

Medicinski podmladak

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Introduction: Peripheral neuroblastic tumours are among the most frequently detected tumours in paediatric patients. A correlation between the aggressiveness of these tumours and their clinical prognosis has been discovered. Neurosecretory granules containing neurotransmitters, an ultrastructural feature of neurons, were found in the cells of peripheral neuroblastic tumours, as well.Aim: The aim of this study was to compare the number of neurosecretory granules found in cells of tumours, with a favourable prognosis to the corresponding number in cells of tumours and with an unfavourable one with the use of transmission electron microscopy (TEM).Material and Methods: Ten tissue biopsies were obtained from paediatric patients diagnosed with peripheral neuroblastic tumours. The tumour samples were first frozen, then fixed in glutaraldehyde, and embedded in epoxy resin. Ultrastructural morphometric analysis was performed on ultrathin sections.Results: When observed under a transmission electron microscope (TEM), neurosecretory granules appear as round structures of a small diameter, with an electron dense centre surrounded by an electron lucent, peripheral halo. It was found that the cells of tumours with an unfavourable prognosis have more neurosecretory granules (141.2 ± 89.18 per 60 cells per sample, on average) in their cytoplasm than the cells of tumours with a favourable one (37.2 ± 41.17 per 60 cells per sample, on average). Conclusion:The larger number of neurosecretory granules found in cells of tumours with an unfavourable prognosis could potentially shed some light on the role these structures play in tumourigenesis of peripheral neuroblastic tumours.

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“…It is well known that oxidative stress is enhanced in NB, and indeed our previous microarray data showed an increase of SOD mRNA expression, as well as altered expression of genes involved in glutathione metabolism [ 24 ]. Moreover, an ultra-structural study on NB primary tumors recently showed consistent auto-phagic vacuoles and abnormality of mitochondria structure in all undifferentiated NB cells [ 31 ]. Therefore, it cannot be excluded that the impaired erythrocyte maturation observed in patients with NB was a peculiar effect consequent to the disruption of mitochondria in this particular lineage, and impairment of mitochondria structure and/or function may be a more general feature of NB tumors.…”

Section: Discussionmentioning

confidence: 99%

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma

et al. 2017

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Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages’ maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cytometry analysis.Gene ontology and disease-associated analysis of the genes significantly under-expressed in BM resident cells from children with localized and metastatic NB, as compared to healthy children, indicated anemia, blood group antigens, and heme and porphyrin biosynthesis as major functional annotation clusters. Accordingly, in children with NB there was a selective impairment of erythrocyte maturation at the ortho-chromic stage that resulted in reduced erythrocyte count in the periphery, regardless of the presence of metastatic cells in the BM. By considering all NB patients, low erythrocyte count at diagnosis associated with worse survival. Moreover, in the subset of metastatic patients, low erythrocyte count, hemoglobin and hematocrit and high red cell distribution width at follow-up also associated with worse outcome.These observations provide an alternative model to the tenet that infiltrating cells inhibit BM functions due to physical occupancy of space and may open a new area of research in NB to understand the mechanism(s) responsible for such selective impairment.

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Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria

Cited by 6 publications

References 36 publications

Activation of the SphK1/ERK/p‑ERK pathway promotes autophagy in colon cancer cells

Activation of the SphK1/ERK/p‑ERK pathway promotes autophagy in colon cancer cells

Ultrastructural morphometry of neurosecretory granules in the neuroblastomas of paediatric patients

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma

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