Cancer stem cell differentiation: TGF beta 1 and versican may trigger molecules for the organization of tumor spheroids

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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.accessioned2019-10-27T22:13:38Z
dc.date.available2019-10-27T22:13:38Z
dc.date.issued2014
dc.departmentEge Üniversitesien_US
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. TGF beta 1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, 1TG beta 3, 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 TG beta 1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGF beta 1 is a triggering molecule, it stimulates versican, Co17A1, ITG beta 3 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.en_US
dc.description.sponsorshipEge University Scientific Research Project FundEge Universityen_US
dc.description.sponsorshipThis study was funded by the Ege University Scientific Research Project Fund.en_US
dc.identifier.doi10.3892/or.2014.3252en_US
dc.identifier.endpage649en_US
dc.identifier.issn1021-335X
dc.identifier.issn1791-2431
dc.identifier.issue2en_US
dc.identifier.pmid24927163en_US
dc.identifier.startpage641en_US
dc.identifier.urihttps://doi.org/10.3892/or.2014.3252
dc.identifier.urihttps://hdl.handle.net/11454/49839
dc.identifier.volume32en_US
dc.identifier.wosWOS:000338908700025en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpandidos Publ Ltden_US
dc.relation.ispartofOncology Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectcancer stem cellsen_US
dc.subjectadhesion moleculesen_US
dc.subjectversicanen_US
dc.subjectTGF beta 1en_US
dc.subjectspheroiden_US
dc.titleCancer stem cell differentiation: TGF beta 1 and versican may trigger molecules for the organization of tumor spheroidsen_US
dc.typeArticleen_US

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