Lau Carol P Y, Wong Kwok Chuen, Huang Lin, Li Gang, Tsui Stephen K W, Kumta Shekhar Madhukar
a Department of Orthopaedics and Traumatology , The Chinese University of Hong Kong , Shatin , NT , Hong Kong .
b Department of Surgery , Prince of Wales Hospital , Shatin , NT , Hong Kong , and.
Connect Tissue Res. 2015 Nov;56(6):493-503. doi: 10.3109/03008207.2015.1075519. Epub 2015 Sep 1.
A major barrier towards the study of the effects of drugs on Giant Cell Tumor of Bone (GCT) has been the lack of an animal model. In this study, we created an animal model in which GCT stromal cells survived and functioned as proliferating neoplastic cells. A proliferative cell line of GCT stromal cells was used to create a stable and luciferase-transduced cell line, Luc-G33. The cell line was characterized and was found that there were no significant differences on cell proliferation rate and recruitment of monocytes when compared with the wild type GCT stromal cells. We delivered the Luc-G33 cells either subcutaneously on the back or to the tibiae of the nude mice. The presence of viable Luc-G33 cells was assessed using real-time live imaging by the IVIS 200 bioluminescent imaging (BLI) system. The tumor cells initially propagated and remained viable on site for 7 weeks in the subcutaneous tumor model. We also tested in vivo antitumor effects of Zoledronate (ZOL) and Geranylgeranyl transferase-I inhibitor (GGTI-298) alone or their combinations in Luc-G33-transplanted nude mice. ZOL alone at 400 µg/kg and the co-treatment of ZOL at 400 µg/kg and GGTI-298 at 1.16 mg/kg reduced tumor cell viability in the model. Furthermore, the anti-tumor effects by ZOL, GGTI-298 and the co-treatment in subcutaneous tumor model were also confirmed by immunohistochemical (IHC) staining. In conclusion, we established a nude mice model of GCT stromal cells which allows non-invasive, real-time assessments of tumor development and testing the in vivo effects of different adjuvants for treating GCT.
缺乏动物模型一直是研究药物对骨巨细胞瘤（GCT）影响的主要障碍。在本研究中，我们创建了一种动物模型，其中GCT基质细胞能够存活并作为增殖性肿瘤细胞发挥作用。使用GCT基质细胞的增殖细胞系创建了稳定的、转导荧光素酶的细胞系Luc-G33。对该细胞系进行了表征，发现与野生型GCT基质细胞相比，其细胞增殖率和单核细胞募集没有显著差异。我们将Luc-G33细胞皮下注射到裸鼠背部或胫骨中。使用IVIS 200生物发光成像（BLI）系统通过实时活体成像评估存活的Luc-G33细胞的存在情况。在皮下肿瘤模型中，肿瘤细胞最初增殖并在原位存活7周。我们还在Luc-G33移植的裸鼠中单独测试了唑来膦酸（ZOL）和香叶基香叶基转移酶-I抑制剂（GGTI-298）的体内抗肿瘤作用或它们的组合。单独使用400µg/kg的ZOL以及400µg/kg的ZOL与1.16mg/kg的GGTI-298联合治疗可降低模型中的肿瘤细胞活力。此外，免疫组织化学（IHC）染色也证实了ZOL、GGTI-298以及联合治疗在皮下肿瘤模型中的抗肿瘤作用。总之，我们建立了GCT基质细胞的裸鼠模型，该模型允许对肿瘤发展进行非侵入性实时评估，并测试不同佐剂治疗GCT的体内效果。
