Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines

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buir.contributor.authorAvcı, M. Ender
buir.contributor.authorKeskus, Ayşe Gökçe
buir.contributor.authorTargen, Seniye
buir.contributor.authorIşılak, M. Efe
buir.contributor.authorÖzturk, Mehmet
buir.contributor.authorAdams, Michelle M.
buir.contributor.authorKonu, Özlen
buir.contributor.authorÇetin-Atalay, Rengül
dc.citation.epage1570-14en_US
dc.citation.issueNumber1en_US
dc.citation.spage1570-1en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorAvcı, M. Enderen_US
dc.contributor.authorKeskus, Ayşe Gökçeen_US
dc.contributor.authorTargen, Seniyeen_US
dc.contributor.authorIşılak, M. Efeen_US
dc.contributor.authorÖztürk, Mehmeten_US
dc.contributor.authorÇetin-Atalay, Rengülen_US
dc.contributor.authorAdams, Michelle M.en_US
dc.contributor.authorKonu, Özlenen_US
dc.date.accessioned2019-02-21T16:02:33Zen_US
dc.date.available2019-02-21T16:02:33Zen_US
dc.date.issued2018en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentInterdisciplinary Program in Neuroscience (NEUROSCIENCE)en_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentAysel Sabuncu Brain Research Center (BAM)en_US
dc.description.abstractAcetylcholinesterase (AChE), an enzyme responsible for degradation of acetylcholine, has been identified as a prognostic marker in liver cancer. Although in vivo Ache tumorigenicity assays in mouse are present, no established liver cancer xenograft model in zebrafish using an ache mutant background exists. Herein, we developed an embryonic zebrafish xenograft model using epithelial (Hep3B) and mesenchymal (SKHep1) liver cancer cell lines in wild-type and ache sb55 sibling mutant larvae after characterization of cholinesterase expression and activity in cell lines and zebrafish larvae. The comparison of fluorescent signal reflecting tumor size at 3-days post-injection (dpi) revealed an enhanced tumorigenic potential and a reduced migration capacity in cancer cells injected into homozygous ache sb55 mutants when compared with the wild-type. Increased tumor load was confirmed using an ALU based tumor DNA quantification method modified for use in genotyped xenotransplanted zebrafish embryos. Confocal microscopy using the Huh7 cells stably expressing GFP helped identify the distribution of tumor cells in larvae. Our results imply that acetylcholine accumulation in the microenvironment directly or indirectly supports tumor growth in liver cancer. Use of this model system for drug screening studies holds potential in discovering new cholinergic targets for treatment of liver cancers.en_US
dc.identifier.doi10.1038/s41598-018-19817-wen_US
dc.identifier.eissn2045-2322en_US
dc.identifier.urihttp://hdl.handle.net/11693/50016en_US
dc.language.isoEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttps://doi.org/10.1038/s41598-018-19817-wen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.source.titleScientific Reportsen_US
dc.titleDevelopment of a novel zebrafish xenograft model in ache mutants using liver cancer cell linesen_US
dc.typeArticleen_US

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Department of Molecular Biology and Genetics
Aysel Sabuncu Brain Research Center (BAM)
Institute of Materials Science and Nanotechnology (UNAM)