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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies

Authors: Marilia Takada, Maciej Parys, Emmalena Gregory-Bryson, Paulo Vilar Saavedra, Matti Kiupel, Vilma Yuzbasiyan-Gurkan

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs.

Methods

The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test.

Results

Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin.

Conclusions

In the present study we demonstrated that a novel canine histiocytic sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans.
Appendix
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Metadata
Title
A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
Authors
Marilia Takada
Maciej Parys
Emmalena Gregory-Bryson
Paulo Vilar Saavedra
Matti Kiupel
Vilma Yuzbasiyan-Gurkan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4132-0

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