Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs

Abstract Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to represent the original tumor in terms of 3D structure, genetic and cellular heterogeneity, but not tumor microenvironment. In this stud...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Mie Naruse, Masako Ochiai, Shigeki Sekine, Hirokazu Taniguchi, Teruhiko Yoshida, Hitoshi Ichikawa, Hiromi Sakamoto, Takashi Kubo, Kenji Matsumoto, Atsushi Ochiai, Toshio Imai
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/fad9475292c8447090559084e9f331ec
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:fad9475292c8447090559084e9f331ec
record_format dspace
spelling oai:doaj.org-article:fad9475292c8447090559084e9f331ec2021-12-02T11:50:30ZRe-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs10.1038/s41598-021-81475-22045-2322https://doaj.org/article/fad9475292c8447090559084e9f331ec2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81475-2https://doaj.org/toc/2045-2322Abstract Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to represent the original tumor in terms of 3D structure, genetic and cellular heterogeneity, but not tumor microenvironment. In this study, we established organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens of colorectal carcinomas (CRCs), and evaluated gene expression profiles in organoids with and without co-culture with CAFs to assess interactions between tumor cells and CAFs in tumor tissues. We found that the expression levels of several genes, which are highly expressed in original CRC tissues, were downregulated in organoids but re-expressed in organoids by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g., REG family and dual oxidases (DUOXs), which are known to have malignant functions, leading tumor cells to proliferative and/or anti-apoptotic states and drug resistant phenotypes. In addition, the degree of differential induction of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case. In conclusion, the co-culture system of CRC organoids with paired CAFs was able to partially reproduce the tumor microenvironment.Mie NaruseMasako OchiaiShigeki SekineHirokazu TaniguchiTeruhiko YoshidaHitoshi IchikawaHiromi SakamotoTakashi KuboKenji MatsumotoAtsushi OchiaiToshio ImaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mie Naruse
Masako Ochiai
Shigeki Sekine
Hirokazu Taniguchi
Teruhiko Yoshida
Hitoshi Ichikawa
Hiromi Sakamoto
Takashi Kubo
Kenji Matsumoto
Atsushi Ochiai
Toshio Imai
Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
description Abstract Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to represent the original tumor in terms of 3D structure, genetic and cellular heterogeneity, but not tumor microenvironment. In this study, we established organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens of colorectal carcinomas (CRCs), and evaluated gene expression profiles in organoids with and without co-culture with CAFs to assess interactions between tumor cells and CAFs in tumor tissues. We found that the expression levels of several genes, which are highly expressed in original CRC tissues, were downregulated in organoids but re-expressed in organoids by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g., REG family and dual oxidases (DUOXs), which are known to have malignant functions, leading tumor cells to proliferative and/or anti-apoptotic states and drug resistant phenotypes. In addition, the degree of differential induction of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case. In conclusion, the co-culture system of CRC organoids with paired CAFs was able to partially reproduce the tumor microenvironment.
format article
author Mie Naruse
Masako Ochiai
Shigeki Sekine
Hirokazu Taniguchi
Teruhiko Yoshida
Hitoshi Ichikawa
Hiromi Sakamoto
Takashi Kubo
Kenji Matsumoto
Atsushi Ochiai
Toshio Imai
author_facet Mie Naruse
Masako Ochiai
Shigeki Sekine
Hirokazu Taniguchi
Teruhiko Yoshida
Hitoshi Ichikawa
Hiromi Sakamoto
Takashi Kubo
Kenji Matsumoto
Atsushi Ochiai
Toshio Imai
author_sort Mie Naruse
title Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
title_short Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
title_full Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
title_fullStr Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
title_full_unstemmed Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs
title_sort re-expression of reg family and duoxs genes in crc organoids by co-culturing with cafs
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/fad9475292c8447090559084e9f331ec
work_keys_str_mv AT mienaruse reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT masakoochiai reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT shigekisekine reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT hirokazutaniguchi reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT teruhikoyoshida reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT hitoshiichikawa reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT hiromisakamoto reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT takashikubo reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT kenjimatsumoto reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT atsushiochiai reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
AT toshioimai reexpressionofregfamilyandduoxsgenesincrcorganoidsbycoculturingwithcafs
_version_ 1718395202674098176