Response to trastuzumab and investigation of expression profiles of matrix metalloproteinase-related proteins in primary breast cancer stem cells

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dc.contributor.authorKoygun, Gozde Kayadibi
dc.contributor.authorKars, Meltem Demirel
dc.contributor.authorEmsen, Ayca
dc.contributor.authorArtac, Hasibe
dc.contributor.authorAksoy, Faruk
dc.contributor.authorCakir, Murat
dc.contributor.authorTavli, Lema
dc.date.accessioned2024-02-23T13:55:59Z
dc.date.available2024-02-23T13:55:59Z
dc.date.issued2021
dc.departmentNEÜen_US
dc.description.abstractBreast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2(+) BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2(+) BCSCs (CD44(+)CD24(-)HER2(+)), HER2(-) BCSCs (CD44(+)CD24(-)HER2(-)), HER2(-) primary culture cells (CD44(+)CD24(+)HER2(-)) and triple positive primary culture cells (CD44(+)CD24(+)HER2(+)). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2(+) BCSCs than in primary culture. HER2(-) BCSCs were more resistant to drugs than HER2(+) BCSCs. Our findings suggest that the presence of HER2(-) BCSCs may be responsible for primary trastuzumab resistance in HER2(+) BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [113S559]; Selcuk University Research Fund [15201017, DPT_2009K121080]en_US
dc.description.sponsorshipThis study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) with project number 113S559 and by Selcuk University Research Fund with project number 15201017 and DPT_2009K121080.en_US
dc.identifier.doi10.1007/s10238-021-00685-0
dc.identifier.endpage456en_US
dc.identifier.issn1591-8890
dc.identifier.issn1591-9528
dc.identifier.issue3en_US
dc.identifier.pmid33471244en_US
dc.identifier.scopus2-s2.0-85099565085en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage447en_US
dc.identifier.urihttps://doi.org/10.1007/s10238-021-00685-0
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11045
dc.identifier.volume21en_US
dc.identifier.wosWOS:000609056900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringer-Verlag Italia Srlen_US
dc.relation.ispartofClinical And Experimental Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBreast Cancer Stem Cellsen_US
dc.subjectCytotoxicityen_US
dc.subjectMmpsen_US
dc.subjectTrastuzumaben_US
dc.subjectAldhen_US
dc.subjectCd44en_US
dc.titleResponse to trastuzumab and investigation of expression profiles of matrix metalloproteinase-related proteins in primary breast cancer stem cellsen_US
dc.typeArticleen_US

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