Comparative Medicine and Integrative Biology, Michigan State University, East Lansing, MI, 48824, USA.
Present address: Royal (Dick) School of Veterinary Studies and the Roslin Institute, Roslin, Midlothian, UK.
BMC Cancer. 2018 Mar 1;18(1):237. doi: 10.1186/s12885-018-4132-0.
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.
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.
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.
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.
组织细胞肉瘤在人类中较为罕见，但在某些犬种中，如伯恩山犬，其发病率相当高。本研究的目的是对一种新型犬组织细胞肉瘤细胞系进行全面鉴定，并将其作为筛选潜在治疗药物的工具。
通过免疫组织化学和流式细胞术技术，对组织细胞肉瘤细胞系进行细胞标志物表达的鉴定。评估肿瘤细胞吞噬珠粒的能力，以及在免疫缺陷小鼠中作为异种移植物生长的能力。我们使用 MTS 增殖测定法研究了一组 13 种化合物的体外细胞毒性活性。采用单因素方差分析比较不同药物的抑制作用，采用 Tukey 检验比较多重均值。
肿瘤细胞表达 CD11c、CD14、CD18、CD45、CD172a、CD204、MHC I 和波形蛋白。暴露于 LPS 后，MHC II 的表达上调。此外，建立的细胞系清楚地显示出与巨噬细胞系阳性对照相似的吞噬活性。接种后 29 天，异种移植小鼠出现可触及的皮下软组织肿块，组织学上与原发性肿瘤相似。达沙替尼，一种酪氨酸激酶泛抑制剂，在临床可达到且可耐受的血浆浓度范围内，显著抑制细胞在体外的生长。与多柔比星联合使用时，达沙替尼的抑制反应增强。
在本研究中，我们证明了一种新型犬组织细胞肉瘤细胞系是评估新治疗方法的有价值工具。肿瘤细胞系对达沙替尼反应良好，这代表了治疗犬类这种恶性肿瘤和人类类似疾病的一种有前途的抗癌策略。
