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

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 fo...

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Autores principales: Takada, Marilia, Parys, Maciej, Gregory-Bryson, Emmalena, Vilar Saavedra, Paulo, Kiupel, Matti, Yuzbasiyan-Gurkan, Vilma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831740/
https://www.ncbi.nlm.nih.gov/pubmed/29490634
http://dx.doi.org/10.1186/s12885-018-4132-0
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author Takada, Marilia
Parys, Maciej
Gregory-Bryson, Emmalena
Vilar Saavedra, Paulo
Kiupel, Matti
Yuzbasiyan-Gurkan, Vilma
author_facet Takada, Marilia
Parys, Maciej
Gregory-Bryson, Emmalena
Vilar Saavedra, Paulo
Kiupel, Matti
Yuzbasiyan-Gurkan, Vilma
author_sort Takada, Marilia
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4132-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-58317402018-03-05 A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies Takada, Marilia Parys, Maciej Gregory-Bryson, Emmalena Vilar Saavedra, Paulo Kiupel, Matti Yuzbasiyan-Gurkan, Vilma BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4132-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-01 /pmc/articles/PMC5831740/ /pubmed/29490634 http://dx.doi.org/10.1186/s12885-018-4132-0 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Takada, Marilia
Parys, Maciej
Gregory-Bryson, Emmalena
Vilar Saavedra, Paulo
Kiupel, Matti
Yuzbasiyan-Gurkan, Vilma
A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title_full A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title_fullStr A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title_full_unstemmed A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title_short A novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
title_sort novel canine histiocytic sarcoma cell line: initial characterization and utilization for drug screening studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831740/
https://www.ncbi.nlm.nih.gov/pubmed/29490634
http://dx.doi.org/10.1186/s12885-018-4132-0
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