Enhanced sensitivity of colon tumour cells to natural killer cell cytotoxicity after mild thermal stress is regulated through HSF1-mediated expression of MICA

dc.authorscopusid23003874000
dc.authorscopusid55422181000
dc.authorscopusid7004356372
dc.authorscopusid6701623438
dc.authorscopusid7006244178
dc.contributor.authorDayanc B.E.
dc.contributor.authorBansal S.
dc.contributor.authorGure A.O.
dc.contributor.authorGollnick S.O.
dc.contributor.authorRepasky E.A.
dc.date.accessioned2024-08-04T19:59:21Z
dc.date.available2024-08-04T19:59:21Z
dc.date.issued2013
dc.departmentİnönü Üniversitesien_US
dc.description.abstractPurpose: Previously we showed that mild thermal stress increased natural killer (NK) cell-mediated tumour cytotoxicity and that this could be blocked by anti-NKG2D or anti-MICA (major histolocompatability complex (MHC) class I related chain A) antibodies. Here, we investigated the role of the transcription factor heat shock factor 1 (HSF1) in thermal regulation of MICA expression in tumour cells in vitro and in vivo. Materials and methods: Hyperthermia experiments were conducted in vitro and in mice using a target temperature of 39.5 °C. Apoptotic cells and NK cells in situ were visualised by use of the TUNEL assay or expression of NKp46 respectively. Using Colo205 cells, HSF1 message was blocked utilising siRNA while luciferase reporter assays were used to measure the activity of the MICA promoter in vitro. Cell surface MICA was measured by flow cytometry. Results: Following whole body hyperthermia (WBH), tumour tissues showed an increase in NK cells and apoptosis. Mild thermal stress resulted in a transient increase in surface MICA and enhanced NK cytotoxicity of the Colo205 colon cancer cell line. Silencing (mRNA) HSF1 expression in Colo205 cells prevented the thermal enhancement of MICA message and surface protein levels, with partial loss of thermally enhanced NK cytotoxicity. Mutations of the HSF1 binding site on the MICA promoter implicated HSF1 in the thermal enhancement of MICA. Some, but not all, patient-derived colon tumour derived xenografts also exhibited an enhanced MICA message expression after WBH. Conclusions: Up-regulation of MICA expression in Colo205 cells and enhanced sensitivity to NK cell killing following mild thermal stress is dependent upon HSF1. © 2013 Informa UK Ltd.en_US
dc.description.sponsorshipDISS0402487; National Institutes of Health, NIH: P01 CA94045, R01 CA71599, R21 CA098852; National Institutes of Health, NIH; Roswell Park Cancer Institute, RPCI: CA16056; Roswell Park Cancer Institute, RPCIen_US
dc.description.sponsorshipThis study was supported by Komen Foundation DISS0402487 and Fulbright Scholarships to BED, National Institutes of Health grants P01 CA94045, R01 CA71599, R21 CA098852, and also Roswell Park Cancer Institute Core grant CA16056. The authors alone are responsible for the content and writing of the paper.en_US
dc.identifier.doi10.3109/02656736.2013.821526
dc.identifier.endpage490en_US
dc.identifier.issn0265-6736
dc.identifier.issue5en_US
dc.identifier.scopus2-s2.0-84881146381en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage480en_US
dc.identifier.urihttps://doi.org/10.3109/02656736.2013.821526
dc.identifier.urihttps://hdl.handle.net/11616/90561
dc.identifier.volume29en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherInforma Healthcareen_US
dc.relation.ispartofInternational Journal of Hyperthermiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCytotoxicityen_US
dc.subjectFever-range hyperthermiaen_US
dc.subjectHSF-1en_US
dc.subjectMICAen_US
dc.subjectNatural killer cellsen_US
dc.subjectNKG2Den_US
dc.titleEnhanced sensitivity of colon tumour cells to natural killer cell cytotoxicity after mild thermal stress is regulated through HSF1-mediated expression of MICAen_US
dc.typeArticleen_US

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