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New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis.

Clark JC, Akiyama T, Dass CR, Choong PF - Cancer Cell Int. (2010)

Bottom Line: 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.All JJ012 periosteal tumours (5/5) resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedics and University of Melbourne Department of Surgery, St Vincent's Health, Melbourne, Australia. sarcoma@bigpond.net.au.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Chondrosarcoma angiogenesis. a) Conditioned media from JJ012 induced a higher number of tube formations compared with FS090 (* p < 0.05). b) Greater angiogenic capacity in JJ012 corresponded with the presence of VEGF on western blotting, in comparison with virtually undetectable VEGF in FS090. The anti-angiogenic protein RECK was prominently expressed by FS090, but not by JJ012.
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Figure 3: Chondrosarcoma angiogenesis. a) Conditioned media from JJ012 induced a higher number of tube formations compared with FS090 (* p < 0.05). b) Greater angiogenic capacity in JJ012 corresponded with the presence of VEGF on western blotting, in comparison with virtually undetectable VEGF in FS090. The anti-angiogenic protein RECK was prominently expressed by FS090, but not by JJ012.

Mentions: Cell-conditioned medium from JJ012 stimulated HMEC-1 cells to form an average number of 64.5 tubes versus 43.8 for FS090 media (p = 0.007) (Fig.3a). The FS090 cultured medium was less angiogenic and this corresponded with virtually absent expression of VEGF on western blotting, in contrast with JJ012. FS090, on the other hand, produced significantly higher levels of RECK protein compared with JJ012 (Fig.3b), and this protein is known to inhibit MMP-2, MMP-9 [18], and possibly also VEGF [19], which may explain the absence of these target proteins in FS090.


New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis.

Clark JC, Akiyama T, Dass CR, Choong PF - Cancer Cell Int. (2010)

Chondrosarcoma angiogenesis. a) Conditioned media from JJ012 induced a higher number of tube formations compared with FS090 (* p < 0.05). b) Greater angiogenic capacity in JJ012 corresponded with the presence of VEGF on western blotting, in comparison with virtually undetectable VEGF in FS090. The anti-angiogenic protein RECK was prominently expressed by FS090, but not by JJ012.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902463&req=5

Figure 3: Chondrosarcoma angiogenesis. a) Conditioned media from JJ012 induced a higher number of tube formations compared with FS090 (* p < 0.05). b) Greater angiogenic capacity in JJ012 corresponded with the presence of VEGF on western blotting, in comparison with virtually undetectable VEGF in FS090. The anti-angiogenic protein RECK was prominently expressed by FS090, but not by JJ012.
Mentions: Cell-conditioned medium from JJ012 stimulated HMEC-1 cells to form an average number of 64.5 tubes versus 43.8 for FS090 media (p = 0.007) (Fig.3a). The FS090 cultured medium was less angiogenic and this corresponded with virtually absent expression of VEGF on western blotting, in contrast with JJ012. FS090, on the other hand, produced significantly higher levels of RECK protein compared with JJ012 (Fig.3b), and this protein is known to inhibit MMP-2, MMP-9 [18], and possibly also VEGF [19], which may explain the absence of these target proteins in FS090.

Bottom Line: 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.All JJ012 periosteal tumours (5/5) resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedics and University of Melbourne Department of Surgery, St Vincent's Health, Melbourne, Australia. sarcoma@bigpond.net.au.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus