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

Abstract Acetylcholinesterase (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 ba...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	M. Ender Avci, Ayse Gokce Keskus, Seniye Targen, M. Efe Isilak, Mehmet Ozturk, Rengul Cetin Atalay, Michelle M. Adams, Ozlen Konu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c46b60246f64a2da15aca1b6e4afe78
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6c46b60246f64a2da15aca1b6e4afe78
record_format	dspace
spelling	oai:doaj.org-article:6c46b60246f64a2da15aca1b6e4afe782021-12-02T15:08:25ZDevelopment of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines10.1038/s41598-018-19817-w2045-2322https://doaj.org/article/6c46b60246f64a2da15aca1b6e4afe782018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19817-whttps://doaj.org/toc/2045-2322Abstract Acetylcholinesterase (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.M. Ender AvciAyse Gokce KeskusSeniye TargenM. Efe IsilakMehmet OzturkRengul Cetin AtalayMichelle M. AdamsOzlen KonuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. Ender Avci Ayse Gokce Keskus Seniye Targen M. Efe Isilak Mehmet Ozturk Rengul Cetin Atalay Michelle M. Adams Ozlen Konu Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
description	Abstract Acetylcholinesterase (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.
format	article
author	M. Ender Avci Ayse Gokce Keskus Seniye Targen M. Efe Isilak Mehmet Ozturk Rengul Cetin Atalay Michelle M. Adams Ozlen Konu
author_facet	M. Ender Avci Ayse Gokce Keskus Seniye Targen M. Efe Isilak Mehmet Ozturk Rengul Cetin Atalay Michelle M. Adams Ozlen Konu
author_sort	M. Ender Avci
title	Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
title_short	Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
title_full	Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
title_fullStr	Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
title_full_unstemmed	Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
title_sort	development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6c46b60246f64a2da15aca1b6e4afe78
work_keys_str_mv	AT menderavci developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT aysegokcekeskus developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT seniyetargen developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT mefeisilak developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT mehmetozturk developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT rengulcetinatalay developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT michellemadams developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines AT ozlenkonu developmentofanovelzebrafishxenograftmodelinachemutantsusinglivercancercelllines
_version_	1718388126125129728

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

Ejemplares similares