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...
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doaj-fad9475292c8447090559084e9f331ec2021-01-24T12:30:58ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111310.1038/s41598-021-81475-2Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFsMie Naruse0Masako Ochiai1Shigeki Sekine2Hirokazu Taniguchi3Teruhiko Yoshida4Hitoshi Ichikawa5Hiromi Sakamoto6Takashi Kubo7Kenji Matsumoto8Atsushi Ochiai9Toshio Imai10Central Animal Division, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteCentral Animal Division, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteDepartment of Diagnostic Pathology, National Cancer Center HospitalDepartment of Diagnostic Pathology, National Cancer Center HospitalDepartment of Clinical Genomics, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteDepartment of Clinical Genomics, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteDepartment of Clinical Genomics, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteDepartment of Clinical Genomics, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteDepartment of Allergy and Clinical Immunology, National Research Institute for Child Health and DevelopmentExploratory Oncology Research & Clinical Trial Center, National Cancer CenterCentral Animal Division, Fundamental Innovative Oncology Core, National Cancer Center Research InstituteAbstract 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.https://doi.org/10.1038/s41598-021-81475-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mie Naruse Masako Ochiai Shigeki Sekine Hirokazu Taniguchi Teruhiko Yoshida Hitoshi Ichikawa Hiromi Sakamoto Takashi Kubo Kenji Matsumoto Atsushi Ochiai Toshio Imai |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-01-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-81475-2 |
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