A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone.
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.
a Department of Orthopaedics and Traumatology , The Chinese University of Hong Kong , Shatin , NT , Hong Kong .
Carol P Y
CP
Lau
a Department of Orthopaedics and Traumatology , The Chinese University of Hong Kong , Shatin , NT , Hong Kong .
Kwok Chuen
KC
Wong
b Department of Surgery , Prince of Wales Hospital , Shatin , NT , Hong Kong , and.
Lin
L
Huang
a Department of Orthopaedics and Traumatology , The Chinese University of Hong Kong , Shatin , NT , Hong Kong .
Gang
G
Li
c School of Biomedical Sciences, The Chinese University of Hong Kong , Shatin , NT , Hong Kong.
Stephen K W
SK
Tsui
a Department of Orthopaedics and Traumatology , The Chinese University of Hong Kong , Shatin , NT , Hong Kong .
Shekhar Madhukar
SM
Kumta
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
D001549:Benzamides; D004164:Diphosphonates; C102521:GGTI 298; D007093:Imidazoles; D000077211:Zoledronic Acid; D008156:Luciferases
Giant cell tumor of bone; animal model; geranylgeranyl transferase-I inhibitor; stromal cells; zoledronate