Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids

Simple item page
dc.contributor.authorOktem G.
dc.contributor.authorSercan O.
dc.contributor.authorGuven U.
dc.contributor.authorUslu R.
dc.contributor.authorUysal A.
dc.contributor.authorGoksel G.
dc.contributor.authorAyla S.
dc.contributor.authorBilir A.
dc.date.accessioned2024-07-22T08:17:14Z
dc.date.available2024-07-22T08:17:14Z
dc.date.issued2014
dc.description.abstractCancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGFβ1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, ITGβ3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TGFβ1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGFβ1 is a triggering molecule, it stimulates versican, Col7A1, ITGβ3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.
dc.identifier.DOI-ID10.3892/or.2014.3252
dc.identifier.issn1021335X
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16993
dc.language.isoEnglish
dc.publisherSpandidos Publications
dc.rightsAll Open Access; Bronze Open Access
dc.subjectAntigens, CD
dc.subjectAntigens, CD44
dc.subjectCell Differentiation
dc.subjectCell Line, Tumor
dc.subjectCollagen Type VII
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGlycoproteins
dc.subjectHumans
dc.subjectIntegrin beta3
dc.subjectMale
dc.subjectNeoplastic Stem Cells
dc.subjectPeptides
dc.subjectProstatic Neoplasms
dc.subjectSpheroids, Cellular
dc.subjectTransforming Growth Factor beta1
dc.subjectTumor Markers, Biological
dc.subjectVersicans
dc.subjectbeta3 integrin
dc.subjectcollagen type 7
dc.subjectcollagen type 7A1
dc.subjectinterstitial collagenase
dc.subjectmatrix metalloproteinase 14
dc.subjectmatrix metalloproteinase 16
dc.subjectnerve cell adhesion molecule
dc.subjectnerve cell adhesion molecule 1
dc.subjectosteopontin
dc.subjecttransforming growth factor beta1
dc.subjectunclassified drug
dc.subjectuvomorulin
dc.subjectversican
dc.subjectbeta3 integrin
dc.subjectCD133 antigen
dc.subjectCD44 protein, human
dc.subjectCOL7A1 protein, human
dc.subjectcollagen type 7
dc.subjectglycoprotein
dc.subjectHermes antigen
dc.subjectITGB3 protein, human
dc.subjectleukocyte antigen
dc.subjectpeptide
dc.subjectTGFB1 protein, human
dc.subjecttransforming growth factor beta1
dc.subjecttumor marker
dc.subjectVCAN protein, human
dc.subjectversican
dc.subjectarticle
dc.subjectcancer stem cell
dc.subjectcarcinogenesis
dc.subjectCDH1 gene
dc.subjectcell differentiation
dc.subjectcell proliferation
dc.subjectCOL7A1 gene
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectgene expression
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunoreactivity
dc.subjectin vitro study
dc.subjectmale
dc.subjectMMP1 gene
dc.subjectMMP16 gene
dc.subjectpriority journal
dc.subjectprostate cancer
dc.subjectprotein expression
dc.subjectsignal transduction
dc.subjectTGF beta1 gene
dc.subjecttumor growth
dc.subjecttumor spheroid
dc.subjectupregulation
dc.subjectVCAN gene
dc.subjectcancer stem cell
dc.subjectcell differentiation
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectmulticellular spheroid
dc.subjectpathology
dc.subjectprostate tumor
dc.subjecttumor cell line
dc.titleCancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids
dc.typeArticle

Files

Collections

Scopus Koleksiyonu