Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice

Abstract A syngeneic mouse model bearing a transplanted tumor is indispensable for the evaluation of the efficacy of immune checkpoint inhibitors (ICIs). However, few syngeneic mouse models of liver cancer are available. We established liver tumor cell lines (MHCF1 and MHCF5) from hepatitis C virus...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Takayoshi Shirasaki, Kazuhisa Murai, Masao Honda, Hikari Okada, Yuika Innami, Atsumu Yamada, Tetsuro Shimakami, Kazunori Kawaguchi, Taro Yamashita, Yoshio Sakai, Shuichi Kaneko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83d1978205734f18b3659fe9a8becfb7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:83d1978205734f18b3659fe9a8becfb7
record_format	dspace
spelling	oai:doaj.org-article:83d1978205734f18b3659fe9a8becfb72021-12-02T17:45:02ZEstablishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice10.1038/s41598-021-92128-92045-2322https://doaj.org/article/83d1978205734f18b3659fe9a8becfb72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92128-9https://doaj.org/toc/2045-2322Abstract A syngeneic mouse model bearing a transplanted tumor is indispensable for the evaluation of the efficacy of immune checkpoint inhibitors (ICIs). However, few syngeneic mouse models of liver cancer are available. We established liver tumor cell lines (MHCF1 and MHCF5) from hepatitis C virus transgenic mice fed an atherogenic high-fat diet. MHCF1 and MHCF5 were successfully transplanted into the subcutaneous space of syngeneic C57BL/6 mice, in addition, they efficiently developed orthotopic tumors in the liver of syngeneic C57BL/6 mice. MHCF5 grew rapidly and showed a more malignant phenotype compared with MHCF1. Histologically, MHCF1-derived tumors were a combined type of hepatocellular carcinoma and MHCF5-derived tumors showed a sarcomatous morphology. Interestingly, MHCF1 and MHCF5 showed different sensitivity against an anti-PD1 antibody and MHCF5-derived tumors were resistant to this antibody. CD8 T cells infiltrated the MHCF1-derived tumors, but no CD8 T cells were found within the MHCF5-derived tumors. Gene expression profiling and whole-exon sequencing revealed that MHCF5 displayed the features of an activated cancer stem cell-like signature of sonic hedgehog and Wnt signaling. Therefore, these cell lines could be useful for the identification of new biomarkers and molecular mechanisms of ICI resistance and the development of new drugs against liver cancer.Takayoshi ShirasakiKazuhisa MuraiMasao HondaHikari OkadaYuika InnamiAtsumu YamadaTetsuro ShimakamiKazunori KawaguchiTaro YamashitaYoshio SakaiShuichi KanekoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takayoshi Shirasaki Kazuhisa Murai Masao Honda Hikari Okada Yuika Innami Atsumu Yamada Tetsuro Shimakami Kazunori Kawaguchi Taro Yamashita Yoshio Sakai Shuichi Kaneko Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
description	Abstract A syngeneic mouse model bearing a transplanted tumor is indispensable for the evaluation of the efficacy of immune checkpoint inhibitors (ICIs). However, few syngeneic mouse models of liver cancer are available. We established liver tumor cell lines (MHCF1 and MHCF5) from hepatitis C virus transgenic mice fed an atherogenic high-fat diet. MHCF1 and MHCF5 were successfully transplanted into the subcutaneous space of syngeneic C57BL/6 mice, in addition, they efficiently developed orthotopic tumors in the liver of syngeneic C57BL/6 mice. MHCF5 grew rapidly and showed a more malignant phenotype compared with MHCF1. Histologically, MHCF1-derived tumors were a combined type of hepatocellular carcinoma and MHCF5-derived tumors showed a sarcomatous morphology. Interestingly, MHCF1 and MHCF5 showed different sensitivity against an anti-PD1 antibody and MHCF5-derived tumors were resistant to this antibody. CD8 T cells infiltrated the MHCF1-derived tumors, but no CD8 T cells were found within the MHCF5-derived tumors. Gene expression profiling and whole-exon sequencing revealed that MHCF5 displayed the features of an activated cancer stem cell-like signature of sonic hedgehog and Wnt signaling. Therefore, these cell lines could be useful for the identification of new biomarkers and molecular mechanisms of ICI resistance and the development of new drugs against liver cancer.
format	article
author	Takayoshi Shirasaki Kazuhisa Murai Masao Honda Hikari Okada Yuika Innami Atsumu Yamada Tetsuro Shimakami Kazunori Kawaguchi Taro Yamashita Yoshio Sakai Shuichi Kaneko
author_facet	Takayoshi Shirasaki Kazuhisa Murai Masao Honda Hikari Okada Yuika Innami Atsumu Yamada Tetsuro Shimakami Kazunori Kawaguchi Taro Yamashita Yoshio Sakai Shuichi Kaneko
author_sort	Takayoshi Shirasaki
title	Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
title_short	Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
title_full	Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
title_fullStr	Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
title_full_unstemmed	Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice
title_sort	establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis c virus transgenic mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/83d1978205734f18b3659fe9a8becfb7
work_keys_str_mv	AT takayoshishirasaki establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT kazuhisamurai establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT masaohonda establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT hikariokada establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT yuikainnami establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT atsumuyamada establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT tetsuroshimakami establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT kazunorikawaguchi establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT taroyamashita establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT yoshiosakai establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice AT shuichikaneko establishmentoflivertumorcelllinesfromatherogenicandhighfatdietfedhepatitiscvirustransgenicmice
_version_	1718379598350123008

Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice

Ejemplares similares