Cargando…
New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis
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 osteoclastoge...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902463/ https://www.ncbi.nlm.nih.gov/pubmed/20584302 http://dx.doi.org/10.1186/1475-2867-10-20 |
_version_ | 1782183764998225920 |
---|---|
author | Clark, Jonathan CM Akiyama, Toru Dass, Crispin R Choong, Peter FM |
author_facet | Clark, Jonathan CM Akiyama, Toru Dass, Crispin R Choong, Peter FM |
author_sort | Clark, Jonathan CM |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2902463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29024632010-07-13 New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis Clark, Jonathan CM Akiyama, Toru Dass, Crispin R Choong, Peter FM Cancer Cell Int Primary research 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. BioMed Central 2010-06-28 /pmc/articles/PMC2902463/ /pubmed/20584302 http://dx.doi.org/10.1186/1475-2867-10-20 Text en Copyright ©2010 Clark et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Primary research Clark, Jonathan CM Akiyama, Toru Dass, Crispin R Choong, Peter FM New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title | New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title_full | New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title_fullStr | New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title_full_unstemmed | New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title_short | New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
title_sort | new clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis |
topic | Primary research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902463/ https://www.ncbi.nlm.nih.gov/pubmed/20584302 http://dx.doi.org/10.1186/1475-2867-10-20 |
work_keys_str_mv | AT clarkjonathancm newclinicallyrelevantorthotopicmousemodelsofhumanchondrosarcomawithspontaneousmetastasis AT akiyamatoru newclinicallyrelevantorthotopicmousemodelsofhumanchondrosarcomawithspontaneousmetastasis AT dasscrispinr newclinicallyrelevantorthotopicmousemodelsofhumanchondrosarcomawithspontaneousmetastasis AT choongpeterfm newclinicallyrelevantorthotopicmousemodelsofhumanchondrosarcomawithspontaneousmetastasis |