Intratibial injection of patient‑derived tumor cells from giant cell tumor of bone elicits osteolytic reaction in nude mouse

Abstract

There have been various reports in the literature of an model for giant cell tumor of bone (GCTB). However, few suitable animal models of GCTB have been established, due to the fact that GCTB contains three histologically different cell types. To the best of our knowledge, injection of patient-derived GCTB cells into bone environment has not been reported until now. In the present study, the biological behavior of GCTB cells in nude mice was investigated through intratibial injection of patient-derived GCTB cells. Patient-derived GCTB cells were obtained from 5 patients who had not undergone chemo- and radiotherapy. Once isolated, the cell suspension was injected into the tibias of nude mice. The growth process was monitored by weekly observation and photographic documentation using X-ray. Four months after injection, nude mice were sacrificed and the injected tibial samples were fixed, and further analyzed using micro-computed tomography (micro-CT), standard histology, tartrate-resistant acid phosphatase (TRAP) staining and mitochondrial immunofluorescence staining. X-ray, micro-CT and standard histology revealed osteolytic destruction in the proximal end of the tibia. TRAP staining identified TRAP-positive, osteoclast-like cells distributed in the bone marrow interface of the lesion area. Anti-human mitochondrial immunofluorescence staining confirmed that the surviving cells in the osteolytic destruction were of human GCTB cell origin. These findings indicate that intratibial injection of patient-derived GCTB cells may elicit osteolytic destruction in nude mice. The results of the current study present a novel animal model for GCTB, opening new perspectives to investigate this disease and develop therapeutic agents.

H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone

“…We comprehensively characterized the epigenetic, transcriptomic (including at the single-cell level) and Golgi proteomics profiles of G34W GCT using primary tumours and isogenic models of tumour-derived cell lines. G34W has been associated with tumourigenesis in previous studies using xenotransplantation of the full tumour (32,33) or transient siRNA knockdown of G34W in GCT-derived cell lines (34). We show that G34W removal is sufficient to prevent tumour formation in vivo, indicating that this mutation is necessary for GCT tumourigenesis.…”

Role of cancer stem cells in the development of giant cell tumor of bone

“…Giant cell tumor of bone (GCTB) consists of three distinct cellular constituents. (1) Circular shaped mononuclear cells, (2) Spindle-like stromal cells, and 3Osteoclast-like multinucleated giant cells [36]. Stromal cells contribute to the involvement of tumor-related myeloid lineage cells and also help in the establishment of osteoclast-like giant cells which lead to the bone desorption processes.…”