Targeting Periostin Expression Makes Pancreatic Cancer Spheroids More Vulnerable to Natural Killer Cells

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dc.authoridAkman, Gizem/0000-0003-4301-5862
dc.authoridUlukaya, Engin/0000-0003-4875-5472
dc.authoridKarakas, Didem/0000-0002-3781-6834
dc.authorwosidKarakas, Didem/L-6682-2018
dc.contributor.authorKarakas, Didem
dc.contributor.authorErkisa, Merve
dc.contributor.authorAkar, Remzi Okan
dc.contributor.authorAkman, Gizem
dc.contributor.authorSenol, Ezgi Yudum
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2024-05-19T14:46:09Z
dc.date.available2024-05-19T14:46:09Z
dc.date.issued2023
dc.departmentİstinye Üniversitesien_US
dc.description.abstractPancreatic cancer (PaCa) characteristically has a dense tumor microenvironment, which results in poor patient prognosis. Pancreatic stellate cells (PSCs) are the most abundant cells in the PaCa microenvironment and the principal source of collagen. Periostin, a matricellular protein, is produced specifically by PSCs and promotes the aggressiveness of PaCa cells by facilitating extracellular collagen assembly. Here, we aimed to decrease extracellular collagen assembly by suppressing periostin, thereby increasing the cytotoxic activity of natural killer (NK) cells. Periostin expression was suppressed in PSCs (called PSC-P) using CRISPR-Cas9. PaCa cells (BxPC-3) were co-cultured with PSC and PSC-P cells in a 3D environment to form tumor spheroids mimicking the tumor microenvironment. The extracellular collagen production of spheroids was evaluated by Masson's trichrome staining. The cytotoxic activity of NK-92 cells was analyzed by flow cytometry and confocal microscopy via CD107a staining. Cell death in BxPC-3 cells was evaluated by measuring Annexin-V and PI positivity using flow cytometry. As a result, periostin suppression decreased extracellular collagen and increased the infiltration of NK-92 cells into spheroids, and induced cell death in PaCa cells. In conclusion, we suggest that periostin might be a therapeutic target for PaCa and further analysis is warranted using in vivo models for proof-of-concept.en_US
dc.description.sponsorshipScientific and Technical Research Council of Turkey (TUBITAK) [118S531]en_US
dc.description.sponsorshipThis work was supported by the Scientific and Technical Research Council of Turkey (TUBITAK) under project number 118S531.en_US
dc.identifier.doi10.3390/biomedicines11020270
dc.identifier.issn2227-9059
dc.identifier.issue2en_US
dc.identifier.pmid36830807en_US
dc.identifier.scopus2-s2.0-85148865058en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org10.3390/biomedicines11020270
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5454
dc.identifier.volume11en_US
dc.identifier.wosWOS:000938442100001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofBiomedicinesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240519_kaen_US
dc.subjectPancreatic Canceren_US
dc.subjectPancreatic Stellate Cellsen_US
dc.subject3d Co-Cultureen_US
dc.subjectCrispren_US
dc.subjectCas9en_US
dc.subjectPeriostinen_US
dc.subjectCollagenen_US
dc.subjectNatural Killer Cellsen_US
dc.titleTargeting Periostin Expression Makes Pancreatic Cancer Spheroids More Vulnerable to Natural Killer Cellsen_US
dc.typeArticleen_US

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