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New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis
Jonathan Cm Clark1, Toru Akiyama, Crispin R Dass
1Department of Orthopaedics and University of Melbourne Department of Surgery, St Vincent's Health, Melbourne, Australia. sarcoma@bigpond.net.au.
Background:
Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy.
Methods:
Two 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.
Results:
JJ012 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.
Conclusions:
The 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.
Insights
A new JJ012 chondrosarcoma mouse model effectively replicates human tumors, showing bone invasion and lung metastasis. This model is crucial for testing new targeted therapies against chondrosarcoma.
Area of Science:
- Orthopedic Oncology
- Cancer Biology
- Translational Research
Background:
- Chondrosarcoma is resistant to conventional adjuvant therapies.
- There is a critical need for clinically relevant animal models to evaluate novel targeted treatments.
Purpose of the Study:
- To establish and characterize new in vivo models of human chondrosarcoma.
- To assess the potential of these models for evaluating targeted therapy efficacy.
Main Methods:
- Two human chondrosarcoma cell lines (JJ012, FS090) were characterized in vitro for proliferation, invasion, and angiogenesis.
- Cell lines were implanted into mouse tibias (intramedullary or periosteal) to evaluate tumor formation, growth, and metastasis.
- Tumor characteristics, including invasion and lung metastasis, were assessed.
Main Results:
- JJ012 cells exhibited higher proliferation, invasion, and colony formation compared to FS090 cells.
- Intratibial and periosteal injections of JJ012 cells successfully formed tumors in mice, while FS090 did not.
- JJ012 tumors showed bone invasion and spontaneous lung metastases, mimicking human chondrosarcoma progression.
Conclusions:
- The JJ012 chondrosarcoma model accurately replicates the site, morphology, and behavior of human tumors.
- This model provides a valuable platform for assessing novel therapeutic agents against chondrosarcoma, particularly for local invasion and metastasis.
