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An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential
Abstract
To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis histology was consistent with OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage cells. The development and use of a more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death from metastasis occurred at a median of 76 days using K7M2 whereas no median was achieved after 140 days using K12. Angiogenic potential, characterized by CD31 and factor VIII staining of primary tumors and pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No significant differences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. This well characterized and relevant model of OSA will be a valuable resource to improve our understanding of the biology and treatment of metastasis in OSA.
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“Companion cell lines with enhanced lung colonization capacity, such as SaOS2-LM7, MG63.3 and 143B 209,210,211 , have enabled the study of metastasis-driving mechanisms 50,212 .”
From Osteosarcoma (2022) · cites this paper as [210]
In the citing paper
“Cultures derived from mice with spontaneous osteosarcoma 210 or from genetically engineered mouse models 100,213 are available to study disease biology or therapeutics in mice with intact immune systems.”
From Osteosarcoma (2022) · cites this paper as [210]
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Metadata
- Authors
- Khanna, C., Prehn, J., Yeung, C., Caylor, J., Tsokos, M., & Helman, L.
- Affiliations
- National Institutes of Health (US)
- Venue
- Clinical & Experimental Metastasis
- Published
- 2000-05
- Volume
- 18
- Issue
- 3
- Pages
- 261-271
- ISSN
- 0262-0898 (ISSN-L)
- 1573-7276
- OpenAlex
- W19745091
- Cited by
- 207
- References
- 42
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 15 · 2019: 6 · 2018: 9 · 2017: 4 · 2016: 11 · 2015: 8 · 2014: 14 · 2013: 15 · 2012: 11
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Clinical & Experimental Metastasis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Health Sciences › Veterinary › Small Animals › Veterinary Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- osteosarcoma, orthotopic tumor model, syngeneic murine model, lung metastasis, tumor angiogenesis, CD31, factor VIII, vascular endothelial growth factor, bone sialoprotein, osteopontin, biglycan, decorin, metastatic potential
- MeSH terms
- Animals, Bone Neoplasms, Female, Lung Neoplasms, Mice, Inbred BALB C, Models, Biological, Osteosarcoma, Survival Analysis, Mice
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