Bone marrow of neuroblastoma patients shows downregulation of <i>CXCL12</i> expression and presence of <i>IFN</i> signature

Scaruffi, Paola; Morandi, Fabio; Gallo, Fabio; Stigliani, Sara; Parodi, Stefano; Moretti, Stefano; Bonassi, Stefano; Fardin, Paolo; Garaventa, Alberto; Zanazzo, Giulio Andrea; Pistoia, Vito; Tonini, Gian Paolo; Corrias, Maria Valeria

doi:10.1002/pbc.23339

Cited by 22 publications

(48 citation statements)

References 43 publications

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“…5,6 Further, stage M patients are characterized by bone marrow (BM) infiltration by NB cells. Multiple evidences suggest that metastatic NB cells are different from primary tumor cell, [7][8][9][10] and that both neoplastic and BMresident cells are influenced by bi-directional signaling in the BM microenvironment. 11 Metastatic NB cells in the BM exploit different mechanisms to escape the control of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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Metastatic diffusion of Neuroblastoma (NB) cells in the bone marrow (BM) represents the most negative prognostic factors for NB patients. Multiple immune escape mechanisms are postulated as responsible. Our working hypothesis is that adenosine (ADO), an immunosuppressive molecule along with the ectoenzymatic pathways (CD39-CD73 and CD38-CD203a/PC-1-CD73) controlling its production, are involved in the dynamics of NB cells in the BM. The results indicate that ectonucleotidases are expressed by i) NB cell lines, ii) metastatic NB cells isolated from NB patients' BM, iii) microvesicles (MV) derived from both NB cell types and iv) resident BM cell populations. BM infiltration by NB cells increased CD203a/PC-1 and CD73 expression on lymphoid and myeloid cells, respectively. Expressions of ectoenzymes and GD2 (NB-associated marker) were higher on MV from NB patients' BM than in controls. Moreover, CD203a/PC-1 expression on BM-derived MV provide a basis for distinguishing NB patients with high or low BM infiltration. ADO production and consumption of related by-products were significantly higher when assessed on NB patients' MV than those from controls. MV isolated from NB patients' BM significantly downregulated in vitro T cell proliferation. Lastly, NB patients with worse prognosis are identified by a high percentage of CD38 + or CD73 + MV in the BM. In conclusion, ectonucleotidases are present and functional on NB cells, as well as in NB-infiltrated BM and in MV derived from BM. It is reasonable that MV are involved in BM infiltration by NB cells. Therefore, targeting these molecules may widen the therapeutic armamentarium for metastatic NB patients. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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“…Scaruffi et al investigated the transcriptome of resident bone marrow cells from localized and metastatic neuroblastoma patients compared to healthy subjects [61]. They found an altered gene expression in bone marrow cells including over-expression of metallothioneins.…”

Section: Other Solid Tumoursmentioning

confidence: 99%

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Microarray analysis of metallothioneins in human diseases AbstractMetallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. 3The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adiposetissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review. List of abbreviations:HCC -hepatocellular carcinoma, HFD -high fat diet, MMP -matrix metalloproteinase, MT -metallothionein, MTF -metal transcription factor, MRE -metal responsive element, ROS -reactive oxygen species.

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“…As demonstrated in other types of tumors, NBL spheroids better recapitulate the salient aspects of in vivo neoplasm growth [288,289]. For instance, Kumar and coworkers [288] have studied the different protein expression profile when NBL cells are cultured in 2D with respect to 3D. The proteomic analysis was performed by 2D gel electrophoresis and followed by mass spectrometry identification.…”

Section: Neuroblastoma Spheroidsmentioning

confidence: 99%

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

Pizzimenti¹

2014

J. Pediatr. Oncol.

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A large body of evidence indicates that three dimensional (3D) cancer models are superior to two-dimensional (2D) ones in better representing the in vivo phenomena. Indeed, 3D models allow recapitulating in vitro the in vivo features observed in solid tumors (e.g. cell polarity, cell-cell/cell-matrix interactions, biochemical/metabolic gradients, anchorage-independent growth and hypoxia). Moreover, it is well established that the microenvironment plays a fundamental role in regulating tumor development and behavior, including drug resistance. Thus, innovative models able to mimic this complexity represent attractive tools in cancer research. In this review article, we provide a comprehensive review of the application of 3D culture systems in pediatrics' cancer research. In particular, 3D in vitro/ex vivo models of the most common pediatric tumors, such as leukemias, lymphomas and malignancies of the nervous system, will be considered.

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Bone marrow of neuroblastoma patients shows downregulation of CXCL12 expression and presence of IFN signature

Cited by 22 publications

References 43 publications

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

Microarray analysis of metallothioneins in human diseases—A review

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

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