A Novel Canine Histiocytic Sarcoma Cell Line: Initial Characterization and Utilization for Drug Screening Studies

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2018 Mar 2

PMID 29490634

Citations 5

Authors

Marilia Takada

Maciej Parys

Emmalena Gregory-Bryson

Paulo Vilar Saavedra

Matti Kiupel

Vilma Yuzbasiyan-Gurkan

Affiliations

Soon will be listed here.

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.

Citing Articles

Canine Histiocytic and Hemophagocytic Histiocytic Sarcomas Display and Extensive /SHP2 Mutations and Respond In Vitro to MEK Inhibition by Cobimetinib.

Yang Y, Engleberg A, Kapoor I, Kitagawa K, Hilburger S, Thaiwong-Nebelung T Genes (Basel). 2024; 15(8).

PMID: 39202410 PMC: 11353564. DOI: 10.3390/genes15081050.

Identification of a Hypomorphic Variant in Bernese Mountain Dogs.

Meek K, Yang Y, Takada M, Parys M, Richter M, Engleberg A Genes (Basel). 2022; 13(10).

PMID: 36292578 PMC: 9601343. DOI: 10.3390/genes13101693.

Activating Mutations in and in Canine Histiocytic Sarcomas.

Takada M, Smyth L, Thaiwong T, Richter M, Corner S, Schall P Genes (Basel). 2019; 10(7).

PMID: 31277422 PMC: 6678586. DOI: 10.3390/genes10070505.

Development of an Orthotopic Intrasplenic Xenograft Mouse Model of Canine Histiocytic Sarcoma and Its Use in Evaluating the Efficacy of Treatment with Dasatinib.

Takada M, Smyth L, Hix J, Corner S, Kiupel M, Yuzbasiyan-Gurkan V Comp Med. 2019; 69(1):22-28.

PMID: 30717820 PMC: 6382049. DOI: 10.30802/AALAS-CM-18-000065.

Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma.

Piegols H, Takada M, Parys M, Dexheimer T, Yuzbasiyan-Gurkan V Oncotarget. 2018; 9(69):33098-33109.

PMID: 30237854 PMC: 6145701. DOI: 10.18632/oncotarget.26006.

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