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Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting

PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these m...

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Autores principales: Aizawa, Yoshihiro, Takada, Kentaro, Aoyama, Jun, Sano, Daisuke, Yamanaka, Shoji, Seki, Masahide, Kuze, Yuta, Ramilowski, Jordan A., Okuda, Ryo, Ueno, Yasuharu, Nojima, Yusuke, Inayama, Yoshiaki, Hatakeyama, Hiromitsu, Hatano, Takashi, Takahashi, Hideaki, Nishimura, Goshi, Fujii, Satoshi, Suzuki, Yutaka, Taniguchi, Hideki, Oridate, Nobuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060313/
https://www.ncbi.nlm.nih.gov/pubmed/36538240
http://dx.doi.org/10.1007/s13402-022-00758-6
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author Aizawa, Yoshihiro
Takada, Kentaro
Aoyama, Jun
Sano, Daisuke
Yamanaka, Shoji
Seki, Masahide
Kuze, Yuta
Ramilowski, Jordan A.
Okuda, Ryo
Ueno, Yasuharu
Nojima, Yusuke
Inayama, Yoshiaki
Hatakeyama, Hiromitsu
Hatano, Takashi
Takahashi, Hideaki
Nishimura, Goshi
Fujii, Satoshi
Suzuki, Yutaka
Taniguchi, Hideki
Oridate, Nobuhiko
author_facet Aizawa, Yoshihiro
Takada, Kentaro
Aoyama, Jun
Sano, Daisuke
Yamanaka, Shoji
Seki, Masahide
Kuze, Yuta
Ramilowski, Jordan A.
Okuda, Ryo
Ueno, Yasuharu
Nojima, Yusuke
Inayama, Yoshiaki
Hatakeyama, Hiromitsu
Hatano, Takashi
Takahashi, Hideaki
Nishimura, Goshi
Fujii, Satoshi
Suzuki, Yutaka
Taniguchi, Hideki
Oridate, Nobuhiko
author_sort Aizawa, Yoshihiro
collection PubMed
description PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. METHODS: Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. RESULTS: Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. CONCLUSION: We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-022-00758-6.
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spelling pubmed-100603132023-03-31 Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting Aizawa, Yoshihiro Takada, Kentaro Aoyama, Jun Sano, Daisuke Yamanaka, Shoji Seki, Masahide Kuze, Yuta Ramilowski, Jordan A. Okuda, Ryo Ueno, Yasuharu Nojima, Yusuke Inayama, Yoshiaki Hatakeyama, Hiromitsu Hatano, Takashi Takahashi, Hideaki Nishimura, Goshi Fujii, Satoshi Suzuki, Yutaka Taniguchi, Hideki Oridate, Nobuhiko Cell Oncol (Dordr) Original Article PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. METHODS: Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. RESULTS: Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. CONCLUSION: We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-022-00758-6. Springer Netherlands 2022-12-20 2023 /pmc/articles/PMC10060313/ /pubmed/36538240 http://dx.doi.org/10.1007/s13402-022-00758-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Aizawa, Yoshihiro
Takada, Kentaro
Aoyama, Jun
Sano, Daisuke
Yamanaka, Shoji
Seki, Masahide
Kuze, Yuta
Ramilowski, Jordan A.
Okuda, Ryo
Ueno, Yasuharu
Nojima, Yusuke
Inayama, Yoshiaki
Hatakeyama, Hiromitsu
Hatano, Takashi
Takahashi, Hideaki
Nishimura, Goshi
Fujii, Satoshi
Suzuki, Yutaka
Taniguchi, Hideki
Oridate, Nobuhiko
Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title_full Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title_fullStr Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title_full_unstemmed Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title_short Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
title_sort establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060313/
https://www.ncbi.nlm.nih.gov/pubmed/36538240
http://dx.doi.org/10.1007/s13402-022-00758-6
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