Skip to main content
Log in

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patientÕs tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Saeter G, Høie J, Stenwig AE et al.1995, Systemic relapse of patients with osteogenic sarcoma: prognostic factors for long term survival. Cancer, 75, 1084–93.

    Google Scholar 

  2. Sharkey FE and Fogh J, 1984, Considerations on the use of nude mice for cancer research. Cancer Metastasis Rev, 3, 341–60.

    Google Scholar 

  3. Fidler IJ, 1986, Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev, 5, 29–49.

    Google Scholar 

  4. Bauer HCF, Brosjö O, Broström L-Å et al.1986, Growth and ploidy of human osteosarcoma xenografts in serial passage in nude mice. Eur J Cancer Clin Oncol, 22, 821–30.

    Google Scholar 

  5. Broström L-Å, Crnalic S, Löfvenberg R, Boquist L and Stenling R, 1996, Growth patterns and cell kinetics of human osteosarcoma xenografts in serial passages in nude mice analysed by in vivolabelling with iododeoxyuridine. J Cancer Res Clin Oncol, 122, 141–6.

    Google Scholar 

  6. Samid D and Mandler R, 1989, Human osteosarcoma cells transformed by ras-oncogenes: a new model for in vivostudies of pulmonary metastasis. Clin Biol, 1, 21–6.

    Google Scholar 

  7. Mandler R, Rimoldi D, Kariko K and Samid D, 1991, Urokinase-type plasminogen activator in experimental metastasis of human osteosarcoma cells. Cancer J, 4, 316–21.

    Google Scholar 

  8. Berlin Ö, Samid D, Donthineni-Rao R et al.1993, Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res, 53, 4890–5.

    Google Scholar 

  9. Manzotti C, Audisio RA and Pratesi G, 1993, Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasion. Clin Exp Metastasis, 11, 5–14.

    Google Scholar 

  10. Eccles SA, Box G, Court W, Sandle J and Dean CJ, 1994, Preclinical models for the evaluation of targeted therapies of metastatic disease. Cell Biophys, 24-25, 279–91.

    Google Scholar 

  11. Fu X, Besterman JM, Monosov A and Hoffman RM, 1991, Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically-intact patient specimens. Proc Natl Acad Sci USA, 88, 9345–9.

    Google Scholar 

  12. Togo S, Shimada H, Kubota T, Moossa AR and Hoffman RM, 1995, Host organ specifically determines cancer progression. Cancer Res, 55, 681–4.

    Google Scholar 

  13. Fu X, Theodorescu D, Kerbel RS and Hoffman RM, 1991, Extensive multi-organ metastasis following orthotopic implantation of histologically-intact human bladder carcinoma tissue in nude mice. Int J Cancer, 49, 938–9.

    Google Scholar 

  14. Wang X, Fu X and Hoffman RM, 1992, A new patientlike metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immuno-deficient mice. Int J Cancer, 51, 992–5.

    Google Scholar 

  15. Furukawa T, Kubota T, Watanabe M, Kitajima M and Hoffman RM, 1993, A novel 'patient-like' treatment model of human pancreatic cancer constructed using orthotopic transplantation of histologically intact human tumor tissue in nude mice. Cancer Res, 53, 3070–2.

    Google Scholar 

  16. Furukawa T, Fu X, Kubota T et al.1993, Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. Cancer Res, 53, 1204–8.

    Google Scholar 

  17. Fu X, Herrera H and Hoffman RM, 1992, Orthotopic growth and metastasis of human prostate carcinoma in nude mice after transplantation of histologicallyintact tissue. Int J Cancer, 52, 987–90.

    Google Scholar 

  18. Astoul P, Colt HG, Wang X, Boutin C and Hoffman RM, 1994, 'Patient-like' nude mouse metastatic model of advanced human pleural cancer. J Cell Biochem, 56, 9–15.

    Google Scholar 

  19. Hoffman RM, 1991, Three-dimensional histoculture: origins and applications in cancer research. Cancer Cells, 3, 86–92.

    Google Scholar 

  20. Aznavoorian S, Murphy AN, Stetler-Stevenson WG and Liotta LA, 1993, Molecular aspects of tumor cell invasion and metastasis. Cancer, 71, 1368–83.

    Google Scholar 

  21. Nicolson GL, 1993, Cancer progression and growth: relationship of paracrine and autocrine growth mechanisms to organ preference of metastasis. Exp Cell Res, 204, 171–80.

    Google Scholar 

  22. Fidler IJ, 1995, Modulation of the organ microenvironment for treatment of cancer metastasis. J Natl Cancer Inst, 87, 1588–92.

    Google Scholar 

  23. Chackal-Roy M, Meimeyer C, Moore M and Zetter BR, 1989, Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. J Clin Invest, 84, 43–50.

    Google Scholar 

  24. Gleave ME, Hsieh JT, von Eschenbach AC and Chung LWK, 1992, Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumor-stromal cell interaction in prostate carcinoma growth and metastasis. J Urol, 147, 1151–9.

    Google Scholar 

  25. Manishen WJ, Sivananthan K and Orr FW, 1986, Resorbing bone stimulates tumor cell growth: a role for the host microenvironment in bone metastasis. Am J Pathol, 123, 39–45.

    Google Scholar 

  26. Orr FW, Millar-Book W and Singh G, 1990, Chemotactic activity of bone and platelet-derived TGF-betafor bone-metastasizing rat Walker 256 carcinosarcoma cells. Invasion Metastasis, 10, 241–52.

    Google Scholar 

  27. Hahn T, Or R, Bruchelt G et al.1996, Control of neuroblastoma cell proliferation and differentiation by human bone marrow. Cancer, 77, 2614–21.

    Google Scholar 

  28. Wagner H, Thomas P, Wolf B et al.1990, Characterisation of the tumorigenic and metastatic potential of a poorly differentiated human colorectal cancer cell line. Invasion Metastasis, 10, 253–66.

    Google Scholar 

  29. Wagner H, Toth CA, Steele GD and Thomas P, 1992, Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production. Clin Exp Metastasis, 10, 25–31. 1

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crnalic, S., Hakansson, I., Boquist, L. et al. A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice. Clin Exp Metastasis 15, 164–172 (1997). https://doi.org/10.1023/A:1018456911823

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018456911823

Navigation