Establishment of a patient-derived xenograft mouse model of pleomorphicleiomyosarcoma

摘要

Soft tissue sarcomas are difficult to treat using chemotherapy owing to a currentdeficiency in candidate drugs for specific targets. Screening candidate compounds andanalyzing therapeutic targets in sarcomas is insufficient, given the lack of anappropriate human sarcoma animal model to accurately evaluate their efficacy, as well asthe lack of an adequate technical protocol for efficient transplantation and engraftmentof sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in thisstudy, we sought to identify the optimal type of sarcoma and develop a protocol forgenerating a PDX model. We characterized a PDX mouse model using histopathological andimmunohistochemical analyses to determine whether it would show pathologicalcharacteristics similar to those of human sarcomas. We achieved engraftment of one of the10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massiveproliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor ofpleomorphic leiomyosarcoma and maintained their histological structure in all passages.Moreover, immunohistochemical analysis revealed the expression of specific markers ofdifferentiation to smooth muscle, which is consistent with the features of leiomyosarcoma.We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at leastone aspect of human sarcomas, and we believe that this model will facilitate thedevelopment of novel therapies for sarcomas.