Experimental models of salivary gland cancer established using organoid culture and patient-derived xenografting

Abstract Purpose: Salivary gland carcinoma (SGC) has poor prognosis depending on the histological subtype. However, due to the scarcity of preclinical experimental models, its molecular biology remains largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study is to generate human SGC experimental models for multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. Methods: Tumor specimens from surgically resected SGC were proceeded for the preparation of PDX and patient-derived organoid (PDO). Specimens from SGC PDX were also proceeded for PDX-derived organoid (PDXO). in vivo tumorigenicity was assessed by orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumor by Immunohistochemistry analysis. The genetic traits of PDO samples were analyzed by RNA-seq. Results: A series of SGC PDOs, PDX and PDXO models using human SGC tumor section for salivary duct carcinoma, mucoepidermoid carcinoma, and myoepithelial carcinoma were successfully generated. Through passaging, each model was confirmed to almost maintain the pathological characteristics of the original tumor and the genetic traits including transcription profiles, genomic variation and the presence of fusion genes of corresponding histological subtypes. Conclusion: We here described success in the generation of in vitro and in vivo SGC models of multiple histological subtypes using organoid culture and PDX, recapitulating the histological and genetical characteristics of original tumor. Thus, our experimental models of SGC could be a powerful resource for the development of novel therapeutic agents and investigating the molecular biology of these malignancies.