Therapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel Therapeutic Approach in Breast Cancer

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dc.authoridKaban, Kübra/0000-0001-7311-7187
dc.authoridŞALVA, EMINE/0000-0002-1159-5850
dc.authoridZhou, Yanjun/0000-0003-0147-9773
dc.authoridSalih, Helmut/0000-0002-6719-1847
dc.authorwosidKaban, Kübra/JFB-1837-2023
dc.authorwosidŞALVA, EMINE/CAH-3062-2022
dc.authorwosidZhou, Yanjun/HPH-9347-2023
dc.contributor.authorKaban, Kuebra
dc.contributor.authorHinterleitner, Clemens
dc.contributor.authorZhou, Yanjun
dc.contributor.authorSalva, Emine
dc.contributor.authorKantarci, Ayse Gulten
dc.contributor.authorSalih, Helmut R.
dc.contributor.authorMaerklin, Melanie
dc.date.accessioned2024-08-04T20:50:13Z
dc.date.available2024-08-04T20:50:13Z
dc.date.issued2021
dc.departmentİnönü Üniversitesien_US
dc.description.abstractSimple Summary Overexpression of the antiapoptotic protein BCL-2 is correlated with estrogen receptor (ER) expression in breast cancer and plays an important role for disease pathophysiology. Here, we conceptualized a novel treatment strategy by targeting ER+ breast cancer with NK cell-derived exosomes used as a carrier for BCL-2 targeted siRNAs. With this new approach, we successfully enhanced killing ability of NK cell derived exosomes by silencing of BCL-2 overexpression. Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in multiple malignancies, including about 85% of patients with estrogen receptor positive (ER+) breast cancer. Besides being studied as a prognostic marker, BCL-2 is investigated as a therapeutic target in ER+ breast cancer. Here, we introduce a new exosome-based strategy to target BCL-2 using genetically modified natural killer (NK) cells. The NK cell line NK92MI was lentivirally transduced to express and load BCL-2 siRNAs (siBCL-2) into exosomes (NKExos) and then evaluated for its potential to treat ER+ breast cancer. Transfected NK92MI cells produced substantial levels of BCL-2 siRNAs, without substantially affecting NK cell viability or effector function and led to loading of siBCL-2 in NKExos. Remarkably, targeting BCL-2 via siBCL-2 NKExos led to enhanced intrinsic apoptosis in breast cancer cells, without affecting non-malignant cells. Together, our prototypical results for BCL-2 in breast cancer provide proof of concept for a novel strategy to utilize NKExos as a natural delivery vector for siRNA targeting of oncogenes.en_US
dc.description.sponsorshipDeutsche Krebshilfe [70113496]; TUBITAK (The Scientific and Technological Research Council of Turkey) [217S455]; Inonu University, Department of Scientific Research Projects [TSA-2017-822]; TUBITAK 2214-A International Research Fellowship Program [1059B141700626]en_US
dc.description.sponsorshipThis research was funded by Deutsche Krebshilfe (70113496), TUBITAK (The Scientific and Technological Research Council of Turkey) (217S455), and Inonu University, Department of Scientific Research Projects (TSA-2017-822). K.K. was funded by the TUBITAK 2214-A International Research Fellowship Program for PhD Students (1059B141700626).en_US
dc.identifier.doi10.3390/cancers13102397
dc.identifier.issn2072-6694
dc.identifier.issue10en_US
dc.identifier.pmid34063475en_US
dc.identifier.scopus2-s2.0-85105731977en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/cancers13102397
dc.identifier.urihttps://hdl.handle.net/11616/99920
dc.identifier.volume13en_US
dc.identifier.wosWOS:000654642700001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofCancersen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNK cellen_US
dc.subjectexosomeen_US
dc.subjectBCL-2en_US
dc.subjectsiRNAen_US
dc.titleTherapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel Therapeutic Approach in Breast Canceren_US
dc.typeArticleen_US

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