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

To provide an investigative tool for the study of osteosarcoma (OSA) biolog y we have developed a syngeneic (balb/c) murine model of OSA, using cell li nes derived from a spontaneously occurring murine OSA (Schmidt et al. Diffe rentiation 1988; 39: 151-60). This model is characterized by orthotopic pri mary tumor growth, a period of minimal residual disease, spontaneous pulmon ary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis his tology was consistent with OSA in human patients. Expression of bone sialop rotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage c ells. The development and use of a more aggressive OSA cell line (K7M2) res ulted in spontaneous metastasis to the lungs in over 90% of mice, whereas m etastases were seen in only 33% of mice when a less aggressive OSA cell lin e (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death fr om 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 d ifferences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. T his well characterized and relevant model of OSA will be a valuable resourc e to improve our understanding of the biology and treatment of metastasis i n OSA.