Clinical & Experimental Metastasis

, Volume 17, Issue 6, pp 501–506 | Cite as

A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies

  • Shu-Fang Jia
  • Laura L. Worth
  • Eugenie S. Kleinerman
Article

Abstract

The purpose of these studies was to develop a metastatic osteosarcoma nude mouse model to evaluate the in vivo efficacy of new therapeutic compounds. Human SAOS-2 osteosarcoma cells (106 cells) were injected i.v. into nude mice. Cells isolated from a rare pulmonary metastases 6 months later were established (SAOS-LM1) in culture and re-injected. This procedure was repeated 5 additional times to produce the SAOS-LM6 cell line. Visible pulmonary nodules were present 8 weeks following i.v. injection of 106 SAOS-LM6 cells as compared to 17 weeks using SAOS-LM2 cells. Microscopic SAOS-LM6 pulmonary metastases were demonstrated at 6 weeks. Administration of adriamycin on week 9 resulted in regression of macroscopic SAOS-LM6 lung tumors. The ability of the model to be used to evaluate the effectiveness of a biologic agent against microscopic disease was also verified. It was concluded that this model can assess therapeutic efficacy and therefore, may have a role in investigating the potential of novel approaches aimed at eliminating pulmonary metastatic osteosarcoma.

lung metastasis mouse model osteosarcoma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Eiber F, Giuliano A, Echardt J et al. Adjuvant chemotherapy for osteosarcoma: A randomized prospective trial. J Clin Oncol 1987; 5: 21–6.Google Scholar
  2. 2.
    Jaffe N. Chemotherapy in osteosarcoma: Experimental and clinical progress in cancer chemotherapy. In Muggia FM(ed): Advances and Controversies. Boston: Martinus Nijhoff Publishers 1986; 223–33.Google Scholar
  3. 3.
    Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of extremity. N Engl J Med 1986; 314: 1600–06.PubMedCrossRefGoogle Scholar
  4. 4.
    Goorin AM, Shuster JJ, Baker A, et al. Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: Results from the multi-institutional osteosarcoma study. J Clin Oncol 1991; 9: 6000–5.Google Scholar
  5. 5.
    Putnam JB, Roth JA, Wesly MN, Survival following aggressive resection of pulmonary metastases from osteogenic sarcoma. Analysis of prognostic factors. Ann Thorac Surg 1986; 36: 516–23.CrossRefGoogle Scholar
  6. 6.
    Jia SF, Zwelling LA, McWatters A, ANT, Kleinerman ES. Interleukin-1? increase the cytotoxicity activity of etoposide against human osteosarcoma cells. J Exp Therap & Oncol (in press).Google Scholar
  7. 7.
    Jia SF, Fan D, Kleinerman ES. Synergestic enhancement of adriamycin cytotoxicity against human osteosarcoma cells by TNFα. Pro Am Assoc Cancer Res 1992; 33: 3301.Google Scholar
  8. 8.
    Jia SF, Worth L, Kleinerman ES. IFNα enhances the cytotoxicactivity of VP-16 and ADR. J Interferon & Cytokine Res 1999; 19: 617–24.CrossRefGoogle Scholar
  9. 9.
    Chen DS, Zhu N-L, Hung G, Skotzko MJ, Hinton DR, Tolo V, Hall FL, Anderson WF, Gordon EM. Retroviral vector-mediated transfer of an antisence cyclin G1 construct inhibits osteosarcoma tumor growth in nude mice. Hum Gene Ther 1997; 8: 1667–74.PubMedGoogle Scholar
  10. 10.
    Meyer WH, Houghton JA, Houghton PJ et al. Development and charecterization of pediatric osteosarcoma xenografts. Cancer Res 1990; 50: 2781–85.PubMedGoogle Scholar
  11. 11.
    Berlin O, Samid D, Donthineni-Rao R et al. Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res 1993; 53: 4890–95.PubMedGoogle Scholar
  12. 12.
    Fidler IJ. Selection of successive tumor lines for metastasis. Nature New Biol 1973; 242: 148–9.PubMedGoogle Scholar
  13. 13.
    Giavazzi R, Campball DE, Jussap JM et al. Metastatic behavior of tumor cells isolated from primary and metastatic human collrectal carcinomas implanted into different sites in nude mice. Cancer Res 1986; 46: 1928–33.PubMedGoogle Scholar
  14. 14.
    Morikawa K, Walker SM, Nakajima M et al. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res 1988; 48: 6863–71.PubMedGoogle Scholar
  15. 15.
    Killion JJ, Kleinerman ES, Wilson MR et al. Sequential therapy with chemotherapeutic drugs and liposome-encapsulated muramyl tripeptide: Determination of potential interaction between these agents. Oncology Res 1992; 4: 413–8.Google Scholar
  16. 16.
    Hudson MM, Snyder JS, Jaffe N, Kleinerman ES. In vitro and in vivo effect of adriamycin therapy on monocyte activation by liposomeencapsulated immunomodualtors. Cancer Res 1988; 48: 5256–63.PubMedGoogle Scholar
  17. 17.
    Kleinerman ES, Gano JB, Johnson DA et al. Efficacy of liposomal muramyl tripeptide (CGP 19835A Lipid) in the treatment of relapsed osteosarcoma. Am J Clin Oncol 1995; 18: 93–9.PubMedGoogle Scholar
  18. 18.
    Samid D, Mandler R. Human osteosarcoma cells transformed by ras oncogenes: a new model for in vivo studies of pulmonary metastasis. Clinic Biotechnol 1989; 1: 21–6.Google Scholar
  19. 19.
    Bell RS, Roth YF, Gebhardt MC et al. Timing of chemotherapy and surgery in a murine osteosarcoma model. Cancer Res 1988; 48: 5533–38, 1988PubMedGoogle Scholar
  20. 20.
    Czitrom AA, Langer F, Gross AE et al. The biology, pathology and immunology of a virus induced rat osteosarcoma. Int Orthop 1980; 4: 157–65.PubMedCrossRefGoogle Scholar
  21. 21.
    Olson HM, Capen CC. Virus-induced animal model of osteosarcoma in the rat. Am J Pathol 1977; 86: 437–52.PubMedGoogle Scholar
  22. 22.
    Cobb LM: Radiation-induced osteosarcoma in the rat as a model for osteosarcoma in man. Br J Cancer 1970; 24: 294–9.PubMedGoogle Scholar
  23. 23.
    Delbruck HG, Allouche M, Jasmin C et al. Bone tumors induced in rats with radioactive cerium. Br J Cancer 1980; 41: 809–15.PubMedGoogle Scholar
  24. 24.
    Witzel JG, Prescher A. An experimental osteosarcoma of athymic nude rat. Invasion Metastasis 1991; 11: 110–5.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Shu-Fang Jia
    • 1
  • Laura L. Worth
    • 2
  • Eugenie S. Kleinerman
    • 1
    • 2
  1. 1.Departments of Cancer BiologyThe University of TexasHoustonUSA
  2. 2.Department of PediatricsThe University of TexasHoustonUSA

Personalised recommendations