TGF-B1-over-expressed adipose stem cells-derived secretome exhibits CD44 suppressor and anti-cancer properties via antagonistic effects against SMAD4 in breast cancer cells

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dc.contributor.authorSalkin, Hasan
dc.contributor.authorYay, Arzu
dc.contributor.authorGokdemir, Nur Seda
dc.contributor.authorGoenen, Zeynep Burgin
dc.contributor.authoroezdamar, Saim
dc.contributor.authorYakan, Birkan
dc.date.accessioned2024-03-13T10:33:40Z
dc.date.available2024-03-13T10:33:40Z
dc.date.issued2022
dc.departmentİstanbul Beykent Üniversitesien_US
dc.description.abstractObjectives: This study aimed to investigate the effect of TGF-B1-transfected adipose-derived mesenchymal stem cell (AD-MSC) conditional medium (TGF-B1-CM) on CD44 expression and biological activities in MCF-7 and MDA-MB-231 cells. Methods: In the study, the experimental groups were created as a standard medium, AD-MSC CM, TGF-B1-CM, and TGF-B1 recombinant protein. The medium and proteins specified in these groups were applied to MCF-7 and MDA-MB-231 cells separately at 24, 48 and 72 hours. Western blot and immunofluorescent staining were performed with antibodies suitable for CD44 and canonical smad signaling pathway analyses between groups. Cellular proliferation in MCF-7 and MDA-MB-231 cells was measured by MTT. Biological activity analyses such as apoptosis, cell cycle, proliferation, DNA damage, and membrane depolarization between groups were tested on the Muse Cell Analyzer using appropriate kits. Cellular migration between groups was determined by showing cells that migrated to the scar area with in vitro scar formation. Statistics were performed with GraphPad Prism 8.02 software. Results: It was determined that TGF-B1-CM activates the smad signaling pathway in MCF-7 and MDA-MB-231 cells. TGF-B1-CM increased pSMAD2/3 expression and decreased SMAD4 expression in breast cancer cells. A decrease in CD44 expression was found at points of increase in pSMAD2/3 expression. Decreased expression of SMAD4 in breast cancer cells with TGF-B1-CM was associated with decreased expression of CD44. In MCF-7 and MDA-MB-231 cells, TGF-B1-CM was found to increase apoptosis, decrease proliferation, disrupt membrane depolarization, and arrest cells at G0/G1 stage. TGF-B1-CM suppressed MCF-7 and MDA-MB-231 migrations. Conclusion: SMAD4-targeted therapeutic strategies may be considered to suppress CD44 expression in breast cancer cells. Both the antitumorigenic factors released by AD-MSCs and the secretomes obtained as a result of supporting these factors with the overexpression of TGF-B1, severely suppressed breast cancer cells. With this study, it was planned to obtain a targeted biological product that suppresses breast cancer cells in vitro.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [219S186]en_US
dc.description.sponsorshipThis study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) with 219S186 project ID. The experiments included in this study were conducted at Erciyes University Genome and Stem Cell Center (GENKOK) . This study was presented as a Ph.D. thesis in Erciyes University, Institute of Health Sciences, Department of Histology-Embryology. The project final report was concluded by TUBITAK on 15.03.2021.en_US
dc.identifier.endpage78en_US
dc.identifier.issn2160-4150
dc.identifier.issue5en_US
dc.identifier.pmid36660741en_US
dc.identifier.startpage64en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12662/4105
dc.identifier.volume11en_US
dc.identifier.wosWOS:000956557600001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherE-Century Publishing Corpen_US
dc.relation.ispartofAmerican Journal Of Stem Cellsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTGF-B1en_US
dc.subjectCD44en_US
dc.subjectadipose-derived mesenchymal stem cellen_US
dc.subjectconditioned mediaen_US
dc.subjectbreast canceren_US
dc.titleTGF-B1-over-expressed adipose stem cells-derived secretome exhibits CD44 suppressor and anti-cancer properties via antagonistic effects against SMAD4 in breast cancer cellsen_US
dc.typeArticleen_US

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