Development of gene expression signatures for mesenchymal stem cells from neuroblastoma patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35133 | GEO | 2012/07/01
SECONDARY ACCESSION(S): PRJNA150813
REPOSITORIES: GEO
Similar Datasets
Project description:To obtain genetic evidence about the interaction between MSCs and metastatic NB cancer cells in bone marrow (BM), we isolated bone marrow-derived MSCs from children with NB and compared their global expression patterns with MSCs obtained from normal pediatric donors using the Agilent 44K microarrays. A total of eight different donors (four NB patients and four healthy donors) were analyzed and three independent microarrays hybridizations were performed for each donor.
2012-06-30 | E-GEOD-35133 | biostudies-arrayexpress
Project description:The bone marrow (BM) is the third most frequent site of metastasis for solid tumors, creating an unfavorable clinical outcome. It provides a unique microenvironment that promotes growth of tumors, however, the role of different BM cells, their molecular features, and their interactions with tumor cells, are poorly defined. Here, we investigate the BM niche in neuroblastoma (NB), a pediatric cancer of the sympathetic nervous system. NB has been molecularly defined at the primary cancer site, yet, the metastatic site is poorly characterized. We performed single-cell transcriptomics (scRNA-seq) and epigenomic profiling (scATAC-seq) of BM aspirates from 11 subjects spanning three major NB subtypes: patients with MYCN amplification (MNA), ATRX mutations (ATRXmut), and cases that lack these alterations (sporadic): NB cases were then compared to five age-matched and metastasis-free BM (controls), followed by in-depth single cell analyses of tissue diversity and cell-cell interactions. We present the first map of the epigenetic and transcriptomic effects of bone marrow metastases. Our analyses demonstrate that tumor cells in the metastatic niche display plasticity that differs among NB subtypes. NB cells via cell-cell interaction signal to the bone marrow microenvironment, rewiring specifically monocytes, which exhibit M1 and M2 features, marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. Our study may provide the basis for a therapeutic approach, targeting tumor-to-microenvironment interactions.
2023-07-20 | PXD036979 | Pride
Project description:Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. At diagnosis, around 70% of patients with metastatic disease present bone-marrow (BM) infiltration; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study was to identify an exosomal signature associated with NB metastatic BM dissemination. Therefore, we characterized the proteomic cargo of exosomes isolated from NB cell lines derived from primary tumor (PT) and BM metastasis. The comparison among all exosomal proteins showed 15 proteins exclusively present in PT, mainly involved in neuronal development, and 6 proteins in BM metastasis-derived exosomes related to cancer progression. Significant proteins obtained with t-test analysis, performed between the 2 groups (PT and BM metastasis), revealed that PT exosomes contain a higher level of proteins involved in extra-cellular matrix (ECM) assembly and adhesion, as well as in neuronal development. Exosomes isolated from BM metastasis showed proteins involved in ameboidal cell migration and mitochondrial activity. This work shows that proteomic profiling of NB-derived exosomes reflects the advanced tumor stage and may be considered as potential tumor biomarker
2018-07-05 | PXD005864 | Pride
Project description:Neuroblastoma (NB) is a pediatric tumor with a heterogeneous presentation at diagnosis. Fifty per cent of patients present with localized disease (stage L1/L2) whereas the other half have metastatic disease (stage M), mainly involving the bone marrow (BM). In these latter patients the physical occupancy of the BM space by metastatic NB cells has been thought to be responsible for impairment of BM function. Here, based on gene expression profiles of BM resident cells obtained in a large number of stage L and stage M NB patients, as compared to gene expression profiles of BM resident cells from healthy subjects, we investigated whether the tumor growth, either at distance or locally, affected hematopoietic lineages' maturation and release of mature hematopoietic cells in the periphery (PB). Our investigation clearly demonstrated that in children with NB, regardless of the presence of metastatic cells in the BM, there was a selective impairment of erythrocyte maturation at the ortho-chromic stage. In the BM, all the other cell lineages were un-affected. The altered erythrocyte maturation resulted in a reduced amount, and increased RWD, of PB erythrocytes. In PB samples from patients with stage L disease a significant increase in the number of mature neutrophils was observed, suggesting that in these NB patients innate immunity was activated. No increase occurred in PB of stage M NB patients. Although the cause of the selective impairment of erythrocyte maturation, as well as that of the activation of innate immunity in stage L NB patients remained elusive, our observations allowed to fully refusing the tenet that BM-infiltrating NB cells affected physiological BM functions due to physical occupancy of the BM space. In addition, these findings open the way to a new area of research not only in NB and other clinically similar pediatric cancers, such as rhabdos and sarcomas, but also in adult cancers metastasizing in the BM. Looking more carefully to the BM microenvironment could help discovering novel targets for innovative therapeutic approaches.
2017-05-31 | GSE90689 | GEO
Project description:Neuroblastoma (NB) is the most common extra cranial solid tumor in infants. Although several risk factors including patient age, disease stage and genetic abnormalities, such as MYCN amplification and 11q deletion, have been shown to predict outcome, the mechanisms responsible for the heterogeneous clinical behavior of this tumor, ranging from spontaneous regression to rapid progression of disease and patient’s death, remain largely unknown. Patients with disseminated disease mainly show metastasis at bone marrow (BM) and bone. The presence of metastasis is an independent unfavorable prognostic factor for NB patients over 18 months of age at diagnosis, whose event-free and overall survivals are grim despite intensive multimodal therapies. We decided to investigate the transcriptome of both NB metastatic cells and resident hematopoietic BM cells to get insight on potential targets for diagnostic, prognostic and therapeutic purposes. Hereby, we report on the results obtained by comparing BM resident hematopoietic cells in the presence and absence of infiltrating NB hematopoietic cells with BM cells from young healthy donors.
2011-09-30 | GSE25624 | GEO
Project description:Neuroblastoma (NB) is the most common extra cranial solid tumor in infants. Although several risk factors including patient age, disease stage and genetic abnormalities, such as MYCN amplification and 11q deletion, have been shown to predict outcome, the mechanisms responsible for the heterogeneous clinical behavior of this tumor, ranging from spontaneous regression to rapid progression of disease and patient’s death, remain largely unknown. Patients with disseminated disease mainly show metastasis at bone marrow (BM) and bone. The presence of metastasis is an independent unfavorable prognostic factor for NB patients over 18 months of age at diagnosis, whose event-free and overall survivals are grim despite intensive multimodal therapies. We decided to investigate the transcriptome of both NB metastatic cells and resident hematopoietic BM cells to get insight on potential targets for diagnostic, prognostic and therapeutic purposes. Hereby, we report on the results obtained by comparing BM resident hematopoietic cells in the presence and absence of infiltrating NB hematopoietic cells with BM cells from young healthy donors. We analyzed gene expression profiles of 40 bone marrow samples: 8 from healthy young donor; 23 from NB patients with stage 1, 2, 3; 9 from NB patients with stage 4.
2011-09-29 | E-GEOD-25624 | biostudies-arrayexpress
Project description:Presence of BM-infiltrating neuroblastoma (NB) cells occurs in about 50% of patients affected by this peculiar pediatric cancer. Children aged more than 18 months at diagnosis with metastatic NB are high-risk patients with 25-30% overall survival at 5 years, despite multimodal aggressive therapy. Little is known about the metastatic process in NB patients. Hereby, we focused on miRNA expression profiles of BM-infiltrating as compared to those of primary NB tumors. For this purpose, we analyzed 22 BM-infiltrating NB cells, 22 primary NB tumors, and 4 paired BM-infiltrating and primary tumor specimens, all from patients with metastatic disease and aged > 18 months at diagnosis. Statistical analysis indicated that in human BM-infiltrating cells miR-659-3p was down-modulated as compared to primary tumors, in all sets of samples. Functional studies in HTLA and SH-SY5Y NB cell lines by miR-659-3p mimic and inhibitors demonstrated that miR-659-3p regulates the expression of the transcription factor CNOT1, that in turn regulates the expression of AU-rich element (ARE)-containing target genes AKT3, BCL2, THSB2 and CYR61, all belonging to the focal adhesion pathway. Indeed, CNOT1 expression was found significantly higher, whereas that of the ARE-containing target genes was significantly lower in BM-infiltrating cells than in primary tumors. Our findings about a role of the focal adhesion pathway, regulated by miR-659-3p through CNOT1, in NB metastatic process are intriguing for the development of new therapeutic strategies aimed to interrupt the metastatic process.
2015-04-20 | GSE65153 | GEO
Project description:It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,…) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1β and TNF-α as compared with normal BM-MSCs. In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs.
2013-03-21 | GSE36474 | GEO
Project description:Objective: Craniofacial bone defects caused by injuries and congenital diseases are a formidable challenge to clinicians. Research has shown promise in using bone marrow mesenchymal stem cells (BM-MSCs) from limb bones for craniofacial bone regeneration; yet little is known about the potential of BM-MSCs from craniofacial bones. This study compared BM-MSCs isolated from limb and craniofacial bones in pigs, a preclinical model closely resembling humans. Design: Bone marrow was aspirated from the tibia and mandible of four-month-old pigs (n=4), followed by BM-MSC isolation, culture-expansion and confirmation by flow cytometry. Proliferation rates were compared using population doubling times. Osteogenic differentiation was evaluated by quantifying alkaline phosphatase (ALP) activity. Total mRNA was extracted from freshly isolated BM-MSCs and analyzed to compare gene expressions of tibial and mandibular BM-MSCs using an Affymetrix GeneChip porcine genome array, followed by real-time RT-PCR evaluation of two neural crest markers. Results: BM-MSCs from both locations expressed MSC markers without expression of hematopoietic markers. Mandibular BM-MSCs proliferated significantly faster than tibial BM-MSCs. Without osteogenic inducers, mandibular BM-MSC alkaline phosphatase activities were 3.3-fold greater than those of tibial origin. Microarray analysis identified 383 differentially expressed genes in mandibular and tibial BM-MSCs, including higher expression of cranial neural crest-related genes nestin and BMP-4 in mandibular BM-MSCs, a trend also confirmed by real-time RT-PCR. Among differently expressed genes, only 47 showed greater than 1.5-fold differences in expression. Conclusions: These data indicate that despite many similarities in gene expression, mandibular BM-MSCs express of number of genes differently than tibial BM-MSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration.
2016-05-14 | GSE81430 | GEO
Project description:Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and re-generative medicine due to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs, but they are now being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have dif-ferent secretion potentials and production, which may influence their therapeutic effects. To prove it, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from 3 different sources: wharton’s jelly (WJ), dental pulp (DP) and bone marrow (BM). Our analysis has focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 human proteins differentially expressed. WJ-MSCs shown the greatest variation compared to the other sources. WJ produced more extra-cellular matrix (ECM) proteins and ECM-affiliated proteins and appeared to more able to modulate the inflammatory and immune response. BM-MSCs display enhanced differentiation and paracrine communication capabilities. DP-MSC appeared to promote exosome production. The results obtained confirm the existence of differences between WJ, DP and BM-MSC and the need to select the MSC origin according to the therapeutic objective sought.
2023-09-20 | PXD043912 | Pride