Abstract 3931: A novel canine histiocytic sarcoma cell line provides a potential path to effective treatments with relevance for translational and comparative studies in humans

Abstract

Abstract Histiocytic sarcoma in people is an uncommon and highly aggressive hematopoietic malignancy that accounts for less than 1% of all non-Hodgkin's lymphomas. Regardless of treatment, patients invariably carry a poor prognosis and a high mortality rate. The low number of cases limits investigations for more efficacious forms of treatment for this disorder. To date, there is no human histiocytic sarcoma cell line available for research purposes. Therefore, the establishment of a representative cell line would be highly beneficial. In the present study, we established a cell line from a tumor in a Bernese mountain dog that was morphologically characterized as a malignant histiocytic sarcoma. The diagnosis was further supported by the positive cellular expression of CD18 and vimentin by immunohistochemistry, and CD11c and MHC II by flow cytometry techniques. Together, the expression of these markers indicated a dendritic cell origin, in accordance to the cell type observed in the majority of histiocytic sarcoma cases in dogs. The established cell line has been maintained in tissue culture for a minimum of 50 passages over 12 months in RPMI 1640 medium supplemented with 15% heat-inactivated fetal bovine serum. Results from a pHrodo™ E. coli Bioparticles® assay indicated that the cells had phagocytic behavior. Furthermore, the cell line was successfully transplantable as a xenograft in immunodeficient mice when injected subcutaneously. A palpable tumor was observed within two weeks of injection and the tumor retrieved from the mice was histopathologically similar to the primary tumor. Finally, we performed cytotoxic assays in vitro with classical chemotherapeutic agents and novel therapeutic drugs, including tyrosine kinase inhibitors. The results from these assays demonstrated that dasatinib, a receptor tyrosine kinase pan-inhibitor, was able to significantly inhibit the growth of the cells in vitro within a clinically achievable, and tolerable plasma concentration. Interestingly, the antiproliferative response to dasatinib was augmented when combined to doxorubicin, a classical chemotherapeutic agent, indicating the potential benefits of drug combination for the treatment of this malignancy. In this study we successfully established a canine histiocytic sarcoma cell line that can be used as model for translational studies for similar disorders in humans. In addition, studies that require a cell line derived from dendritic cells can also benefit from this new established cell line. Citation Format: Marilia Takada, Maciej Parys, Emmalena Gregory-Bryson, Vilma Yuzbasiyan-Gurkan. A novel canine histiocytic sarcoma cell line provides a potential path to effective treatments with relevance for translational and comparative studies in humans. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3931. doi:10.1158/1538-7445.AM2014-3931