Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma

Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately...

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Bibliographic Details
Published in:Journal of Toxicologic Pathology 2021, Vol.34(1), pp.89-93
Main Authors: Shimada, Yasuhiro, Naito, Tomoharu, Hayashi, Takuo, Saito, Tsuyoshi, Suehara, Yoshiyuki, Kakinuma, Chihaya, Nozaki, Yuji, Takagi, Hisayoshi, Yao, Takashi
Format: Article
Language:English
Subjects:
Animal models
Chemical compounds
Chemotherapy
Drug development
Drug screening
Immunosuppressive agents
mouse model
Muscles
Original
patient-derived xenograft (PDX)
Pharmacology
pleomorphic leiomyosarcoma (PLMS)
Sarcoma
Smooth muscle
Soft tissues
Transplantation
Tumors
Xenografts
Xenotransplantation
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Summary:Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas.
ISSN:0914-9198
1881-915X
1347-7404
DOI:10.1293/tox.2020-0061