title: Xenograft models for undifferentiated pleomorphic sarcoma not otherwise specified are essential for preclinical testing of therapeutic agents.
abstract: Undifferentiated pleomorphic sarcoma not otherwise specified belongs to the heterogeneous group of soft tissue tumors. It is preferentially located in the upper and lower extremities of the body, and surgical resection remains the only curative treatment. Preclinical animal models are crucial to improve the development of novel chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma. However, this approach has been hampered by the lack of reproducible animal models. The present study established two xenograft animal models generated from stable non-clonal cell cultures, and investigated the difference in chemotherapeutic effects on tumor growth between undifferentiated pleomorphic sarcomain vivoandin vitro. The cell cultures were generated from freshly isolated tumor tissues of two patients with undifferentiated pleomorphic sarcoma. For thein vivoanalysis, these cells were injected subcutaneously into immunodeficient mice. The mice were monitored for tumor appearance and treated with the most common or innovative chemotherapeutic agents available to date. Furthermore, the same drugs were administered toin vitrocell cultures. The most effective tumor growth inhibitionin vitrowas observed with doxorubicin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat. In thein vivoxenograft mouse model, the combination of doxorubicin and the tyrosine kinase inhibitor pazopanib induced a significant tumor reduction. By contrast, treatment with vorinostat did not reduce the tumor growth. Taken together, the results obtained from drug testingin vitrodiffered significantly from thein vivoresults. Therefore, the novel and reproducible xenograft animal model established in the present study demonstrated thatin vivomodels are required to test potential chemotherapeutic agents for the treatment of undifferentiated pleomorphic sarcoma prior to clinical use, since animal models are more similar to humans, compared within vitrocell cultures.
authors.affiliation: Institute of Pathology, Saarland University Medical Center, Homburg, Saarland D-66421, Germany; Interdisciplinary Sarcoma Working Group, Center of Orthopaedic and Trauma Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-5513, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Becker
authors.affiliation: III Department of Internal Medicine, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-55131, Germany.
authors.forename: Claudine
authors.initials: C
authors.lastname: Graf
authors.affiliation: Interdisciplinary Sarcoma Working Group, Center of Orthopaedic and Trauma Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-5513, Germany; Department for Orthopaedic and Trauma Surgery, University Hospital Mannheim, Mannheim, Baden-Württemberg D-68167, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Tonak
authors.affiliation: Institute for Immunology, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-55131, Germany.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.affiliation: Institute for Immunology, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-55131, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University Medical Center, Homburg, Saarland D-66421, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Institute of Pathology, Saarland University Medical Center, Homburg, Saarland D-66421, Germany.
authors.forename: Rainer M
authors.initials: RM
authors.lastname: Bohle
authors.affiliation: III Department of Internal Medicine, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-55131, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Theobald
authors.affiliation: Interdisciplinary Sarcoma Working Group, Center of Orthopaedic and Trauma Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-5513, Germany.
authors.forename: Pol-Maria
authors.initials: PM
authors.lastname: Rommens
authors.affiliation: Interdisciplinary Sarcoma Working Group, Center of Orthopaedic and Trauma Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-5513, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Proschek
authors.affiliation: III Department of Internal Medicine, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Rhineland-Palatinate D-55131, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wehler
keywords: HDAC inhibitor; animal model; doxorubicin; pazopanib; pleomorphic sarcoma; xenograft