Abstract
BackgroundChondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy.MethodsTwo human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases.ResultsJJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5) resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases.ConclusionsThe established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.
Highlights
Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy
Cells were cultured in DMEM (Invitrogen, Carlsbad, CA) supplemented with 10% fetal calf serum (FCS) and 1% antimicrobials, and were removed from 75 ml culture flasks by incubating in 2 ml of trypsin/EDTA with type I collagenase (1 mg/ml) (Sigma-Aldrich, Australia) at 37°C for 5 minutes
Chondrosarcoma cell-conditioned media was harvested after exposure to cells (JJ012 or FS090) at 80% confluence for 48 h under the conditions described
Summary
Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Chondrosarcoma is a common primary bone sarcoma, which is second only to osteosarcoma in incidence. It most often arises in the over 40 age group [1], and is associated with significant mortality and morbidity [2,3]. A significant proportion of chondrosarcomas are low-grade, these are well-known to recur locally, even 5 years or more following the initial tumour resection. This often requires further wide-margin surgery, with the potential for significant morbidity [4]. The reasons for this are yet to be fully defined, it is thought that a variety of factors are contributory, including p-glycoprotein expression [7]
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