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Open Access 20-12-2022 | Salivary Gland Cancer | Original Article

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

Authors: Yoshihiro Aizawa, Kentaro Takada, Jun Aoyama, Daisuke Sano, Shoji Yamanaka, Masahide Seki, Yuta Kuze, Jordan A. Ramilowski, Ryo Okuda, Yasuharu Ueno, Yusuke Nojima, Yoshiaki Inayama, Hiromitsu Hatakeyama, Takashi Hatano, Hideaki Takahashi, Goshi Nishimura, Satoshi Fujii, Yutaka Suzuki, Hideki Taniguchi, Nobuhiko Oridate

Published in: Cellular Oncology | Issue 2/2023

Abstract

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.

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Title: Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting
Authors: Yoshihiro Aizawa
Kentaro Takada
Jun Aoyama
Daisuke Sano
Shoji Yamanaka
Masahide Seki
Yuta Kuze
Jordan A. Ramilowski
Ryo Okuda
Yasuharu Ueno
Yusuke Nojima
Yoshiaki Inayama
Hiromitsu Hatakeyama
Takashi Hatano
Hideaki Takahashi
Goshi Nishimura
Satoshi Fujii
Yutaka Suzuki
Hideki Taniguchi
Nobuhiko Oridate
Publication date: 20-12-2022
Publisher: Springer Netherlands
Keywords: Salivary Gland Cancer
Salivary Gland Cancer
Published in: Cellular Oncology / Issue 2/2023
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-022-00758-6

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