Enrichment of neural-related genes in human mesenchymal stem cells from neuroblastoma patients

Rodriguez-Milla,Miguel  Ángel; Mirones,Isabel; Mariñas-Pardo,Luis; Melen,Gustavo   J.; Cubillo,Isabel; Ramírez,Manuel; García-Castro,Javier

doi:10.3892/ijmm.2012.1008

Enrichment of neural-related genes in human mesenchymal stem cells from neuroblastoma patients

Authors:
- Miguel Ángel Rodriguez-Milla
- Isabel Mirones
- Luis Mariñas-Pardo
- Gustavo J. Melen
- Isabel Cubillo
- Manuel Ramírez
- Javier García-Castro
View Affiliations

Affiliations: Cellular Biotechnology Unit, Institute of Health Carlos III, Majadahonda, Madrid, Spain, Department of Oncohematology, Hospital Niño Jesús, Madrid, Spain
Published online on: May 22, 2012 https://doi.org/10.3892/ijmm.2012.1008
Pages: 365-373

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Neuroblastoma (NB) is one of the most common pediatric solid tumors and, like most human cancers, is characterized by a broad variety of genomic alterations. Although mesenchymal stem cells (MSCs) are known to interact with cancer cells, the relationship between MSCs and metastatic NB cancer cells in bone marrow (BM) is unknown. To obtain genetic evidence about this interaction, we isolated ΒΜ-derived MSCs from children with NB and compared their global expression patterns with MSCs obtained from normal pediatric donors, using the Agilent 44K microarrays. Significance analysis of microarray results with a false discovery rate (FDR) <5% identified 496 differentially expressed genes showing either a 2-fold upregulation or downregulation between both groups of samples. Comparison of gene ontology categories of differentially expressed genes revealed the upregulation of genes categorized as ‘neurological system process’, ‘cell adhesion’, ‘apoptosis’, ‘cell surface receptor linked signal transduction’, ‘intrinsic to membrane’ and ‘extracellular region’. Among the downregulated genes, several immunology-related terms were the most abundant. These findings provide preliminary genetic evidence of the interaction between MSCs and NB cancer cells in ΒΜ as well as identify relevant biological processes potentially altered in MSCs in response to NB.

View Figures

View References

1.	A EhningerA TrumppThe bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move inJ Exp Med208421428201110.1084/jem.2011013221402747
2.	PJ MishraJW GlodD BanerjeeMesenchymal stem cells: flip side of the coinCancer Res6912551258200910.1158/0008-5472.CAN-08-356219208837
3.	E HiyamaK HiyamaH YamaokaT SuedaCP ReynoldsT YokoyamaExpression profiling of favorable and unfavorable neuroblastomasPediatr Surg Int203338200410.1007/s00383-003-1077-314691637
4.	N KameiK HiyamaH YamaokaEvaluation of genes identified by microarray analysis in favorable neuroblastomaPediatr Surg Int25931937200910.1007/s00383-009-2448-119701758
5.	QR ChenYK SongLR YuGlobal genomic and proteomic analysis identifies biological pathways related to high-risk neuroblastomaJ Proteome Res9373382201010.1021/pr900701v19921788
6.	F AbelD DaleviM NethanderA 6-gene signature identifies four molecular subgroups of neuroblastomaCancer Cell Int119201110.1186/1475-2867-11-921492432
7.	A AbarrategiL Marinas-PardoI MironesE RinconJ Garcia-CastroMesenchymal niches of bone marrow in cancerClin Transl Oncol13611616201110.1007/s12094-011-0706-x21865132
8.	G GrisendiR BussolariE VeronesiUnderstanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the MesenkillersAm J Cancer Res1787805201122016827
9.	M MaJY YeR DengCM DeeGC ChanMesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signalingCancer Lett312110201110.1016/j.canlet.2011.06.02821906874
10.	I AiroldiC CoccoF MorandiI PrigioneV PistoiaCXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrowCancer Immunol Immunother57541548200810.1007/s00262-007-0392-217786442
11.	M DominiciK Le BlancI MuellerMinimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy8315317200610.1080/14653240600855905
12.	VG TusherR TibshiraniG ChuSignificance analysis of microarrays applied to the ionizing radiation responseProc Natl Acad Sci USA9851165121200110.1073/pnas.09106249811309499
13.	AI SaeedV SharovJ WhiteTM4: a free, open-source system for microarray data management and analysisBiotechniques34374378200312613259
14.	dW HuangBT ShermanQ TanDAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene listsNucleic Acids Res35W169W1752007
15.	T HahnR OrG BrucheltControl of neuroblastoma cell proliferation and differentiation by human bone marrowCancer7726142621199610.1002/(SICI)1097-0142(19960615)77:12%3C2614::AID-CNCR27%3E3.0.CO;2-U8640713
16.	JD WaltonBA SpenglerJL BiedlerWL GeraldNKV CheungRA RossMicroarray analyses of human neuroblastoma stem cells identifies genes associated with malignancyProc Amer Assoc Cancer Res20056882005
17.	C RozzoV ChiesaM PonzoniIntegrin upregulation as marker of neuroblastoma cell differentiation: correlation with neurite extensionCell Death Differ4713724199710.1038/sj.cdd.440030416465284
18.	I MiyakeM OhiraA NakagawaraR SakaiDistinct role of ShcC docking protein in the differentiation of neuroblastomaOncogene28662673200910.1038/onc.2008.41318997821
19.	S GeryCL SawyersDB AgusJW SaidHP KoefflerTMEFF2 is an androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cellsOncogene2147394746200210.1038/sj.onc.120514212101412
20.	K LinJR TaylorTD WuTMEFF2 is a PDGF-AA binding protein with methylation-associated gene silencing in multiple cancer types including gliomaPLoS One6e18608201110.1371/journal.pone.001860821559523
21.	S GesierichC ParetD HildebrandColocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motilityClin Cancer Res1128402852200510.1158/1078-0432.CCR-04-193515837731
22.	M ZöllerTetraspanins: push and pull in suppressing and promoting metastasisNat Rev Cancer94055200919078974
23.	K KoshikawaH OsadaK KozakiSignificant upregulation of a novel gene, CLCP1, in a highly metastatic lung cancer subline as well as in lung cancers in vivoOncogene2128222828200210.1038/sj.onc.120540511973641
24.	M KimKT LeeHR JangEpigenetic downregulation and suppressive role of DCBLD2 in gastric cancer cell proliferation and invasionMol Cancer Res6222230200810.1158/1541-7786.MCR-07-014218314483
25.	AA RizvanovME YalvaçAK ShafigullinaInteraction and self-organization of human mesenchymal stem cells and neuro-blastoma SH-SY5Y cells under co-culture conditions: A novel system for modeling cancer cell micro-environmentEur J Pharm Biopharm76253259201010.1016/j.ejpb.2010.05.012
26.	DJ MaltmanSA HardySA PrzyborskiRole of mesenchymal stem cells in neurogenesis and nervous system repairNeurochem Int59347356201121718735
27.	W DuN HozumiM SakamotoJ HataT YamadaReconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cellsAm J Pathol17311531164200810.2353/ajpath.2008.07030918772334
28.	Y TakashimaT EraK NakaoNeuroepithelial cells supply an initial transient wave of MSC differentiationCell12913771388200710.1016/j.cell.2007.04.02817604725
29.	S YonaHH LinWO SiuS GordonM StaceyAdhesion-GPCRs: emerging roles for novel receptorsTrends Biochem Sci33491500200810.1016/j.tibs.2008.07.00518789697
30.	T IguchiK SakataK YoshizakiK TagoN MizunoH ItohOrphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathwayJ Biol Chem2831446914478200810.1074/jbc.M70891920018378689
31.	L XuRO HynesGPR56 and TG2: possible roles in suppression of tumor growth by the microenvironmentCell Cycle6160165200710.4161/cc.6.2.376017314516
32.	S ShashidharG LorenteU NagavarapuGPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesionOncogene2416731682200510.1038/sj.onc.120839515674329
33.	WA LamL CaoV UmeshAJ KeungS SenS KumarExtracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expressionMol Cancer935201010.1186/1476-4598-9-3520144241
34.	S MussunoorGI MurrayThe role of annexins in tumor development and progressionJ Pathol216131140200810.1002/path.240018698663
35.	Y SoharaH ShimadaC MinkinA Erdreich-EpsteinJA NoltaYA DeClerckBone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cellsCancer Res6511291135200510.1158/0008-5472.CAN-04-285315734993
36.	PD JohannM VaeglerF GiesekeTumor stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicityBMC Cancer10501201010.1186/1471-2407-10-50120858262