An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential

C. Khanna, J. Prehn, C. Yeung, J. Caylor, M. Tsokos, Lee J. Helman

Research output: Contribution to journalArticle

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 (flt 1, flt 4, 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.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalClinical and Experimental Metastasis
Volume18
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Osteosarcoma
Lung
Neoplasm Metastasis
Cell Line
Vascular Endothelial Growth Factor Receptor-3
Integrin-Binding Sialoprotein
Neoplasms
Osteopontin
Factor VIII
Residual Neoplasm
Vascular Endothelial Growth Factor A
Histology
Staining and Labeling
Bone and Bones
Growth
Genes

Keywords

  • Cancer
  • Model
  • Murine
  • Orthotopic
  • Osteosarcoma
  • Spontaneous pulmonary metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. / Khanna, C.; Prehn, J.; Yeung, C.; Caylor, J.; Tsokos, M.; Helman, Lee J.

In: Clinical and Experimental Metastasis, Vol. 18, No. 3, 2000, p. 261-271.

Research output: Contribution to journalArticle

Khanna, C. ; Prehn, J. ; Yeung, C. ; Caylor, J. ; Tsokos, M. ; Helman, Lee J. / An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. In: Clinical and Experimental Metastasis. 2000 ; Vol. 18, No. 3. pp. 261-271.
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