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

Abstract

BackgroundHistiocytic 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.MethodsThe 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.ResultsNeoplastic 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.ConclusionsIn 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 materialThe online version of this article (10.1186/s12885-018-4132-0) contains supplementary material, which is available to authorized users.

Targeting MEK in a Translational Model of Histiocytic Sarcoma

“…Two cell lines originated from BMD (BD and OD), the breed with the highest incidence of HS, and one from a Rottweiler (PJ). A comprehensive characterization of the BD cell line was recently published by our group (44).To confirm the histiocytic phenotype, we used two markers that are routinely used to diagnose canine HS: CD18 (integrin beta chain beta 2) and CD204 (class A macrophage scavenger receptor; refs. 25,28,29,40,42).…”

“…To date, there is no human HS cell line available for study. We have derived and characterized canine HS cell lines, one of which has been described in detail (44). We were able to capitalize on this opportunity by using HS cell lines established from dogs as tools for the systematic discovery of novel treatment approaches.…”

Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma

“…Additionally, cats clear some drugs more slowly, such as acetaminophen, propofol, carprofen, and acetylsalicylic acid, than humans and dogs due to relative deficiencies in UDP-glucuronosyltransferase enzymes, N-acetyltransferase, and thiopurine methyltransferase; thus, drugs undergoing metabolism via conjugation may require dosage adjustments in comparison to humans and dogs to avoid toxicity in cats [ 42 ]. These differences, however, do not diminish the potential value of using FOSCC as a model for SCCHN as animal models of human disease have been demonstrated to provide translational insight into treatments for human diseases [ 43 ].…”

Sarcoma Histiocítico Com Múltiplas Localizações Em Um Cão

“…Estudos recentes mostram o complexo sarcoma histiocítico indicando expressão de marcadores celulares que levam a crer que as células dessa neoplasia são provenientes de células dendríticas (TAKADA et al, 2018). Esse sarcoma possui células proliferadas de formato ovoide a reniforme, muitas vezes apresentando células binucleadas e gigantes.…”

“…Algumas raças apresentam predisposição para o aparecimento da neoplasia, como o Bernese Mountain, Golden Retriver, Flat-Coated Retriever e Rottweiller (HENDRICK, 2017). A predisposição genética dessas raças tem sido estudada, tanto para o melhor entendimento do tumor, quanto para auxiliar no conhecimento dessa neoplasia em humanos (HEDAN et al, 2011;TAKADA et al, 2018).…”