Skip to main content

Advertisement

Log in

Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical relevance and applicability for drug testing

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Osteosarcoma cells derived from patients have been isolated and subsequently cultured for the past 35 years. To date though, there have been no major break-throughs in the development of a model for osteosarcoma that uses orthotopic implantation of human osteosarcoma cells and that closely emulates the clinical progression of this debilitating and fatal disease. Such a model is long overdue given the devastating demographics (second highest cause of cancer-related death in the paediatric age group) of the ailment and the lack of solid options for control, if not cure, for the disease, as it also is the most common primary tumour of bone. Only then can more robust R & D be undertaken in the search for efficacious anti-osteosarcoma agents. This review tackles this conundrum and lists the variety of models (that use human osteosarcoma cells) available and the types of studies performed with these.

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.

Similar content being viewed by others

References

  • Arnstein P, Taylor DO, Nelson-Rees WA, Huebner RJ, Lennette EH (1974) Propagation of human tumors in antithymocyte serum-treated mice. J Natl Cancer Inst 52(1):71–84

    PubMed  CAS  Google Scholar 

  • Berlin O, Samid D, Donthineni-Rao, Akeson W, Amiel D, Woods V (1993) Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into the bone of athymic mice. Cancer Res 53:4890–4895

    PubMed  CAS  Google Scholar 

  • de Bock CE, Lin Z, Itoh T, Morris D, Murrell G, Wang Y (2005) Inhibition of urokinase receptor gene expression and cell invasion by anti-uPAR DNAzymes in osteosarcoma cells. FEBS J 272(14):3572–3582

    Article  PubMed  CAS  Google Scholar 

  • Dass CR, Nadesapillai AW, Fisher JL, Howard M, Zhou H, Choong PFM (2006) Downregulation of uPAR confirms link in osteosarcoma. Clin Exp Metastasis 23 (in press)

  • Chen DS, Zhu NL, Hung G, Skotzko MJ, Hinton DR, Tolo V, Hall FL, Anderson WF, Gordon EM (1997) Retroviral vector-mediated transfer of an antisense cyclin G1 construct inhibits osteosarcoma tumor growth in nude mice. Hum Gene Ther 8(14):1667–1674

    PubMed  CAS  Google Scholar 

  • Chen X, Li Y, Xiong K, Aizicovici S, Xie Y, Zhu Q, Sturtz F, Shulok J, Snodgrass R, Wagner TE, Platika D (1998) Cancer gene therapy by direct tumor injections of a nonviral T7 vector encoding a thymidine kinase gene. Hum Gene Ther 9(5):729–736

    PubMed  CAS  Google Scholar 

  • Clapham P, Nagy K, Cheingsong-Popov R, Exley M, Weiss RA (1983) Productive infection and cell-free transmission of human T-cell leukemia virus in a nonlymphoid cell line. Science 222(4628):1125–1127

    Article  PubMed  CAS  Google Scholar 

  • Fisher JL, Mackie PS, Howard ML, Zhou H, Choong PF (2001) The expression of urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model. Clin Cancer Res 1654(7):1654–1660

    Google Scholar 

  • Fogh J, Fogh JM, Orfeo T (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 59(1):221–226

    PubMed  CAS  Google Scholar 

  • Friedlaender GE, Mitchell MS (1976) A virally induced osteosarcoma in rats. A model for immunological studies of human osteosarcoma. J Bone Joint Surg Am 58(3):295–302

    PubMed  CAS  Google Scholar 

  • Ho WZ, Harouse JM, Rando RF, Gonczol E, Srinivasan A, Plotkin SA (1990) Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. J Gen Virol 71(Pt 1):97–103

    Article  PubMed  CAS  Google Scholar 

  • Jia SF, Worth LL, Kleinerman ES (1999) A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies. Clin Exp Metastasis 17(6):501–506

    Article  PubMed  CAS  Google Scholar 

  • Jia SF, Worth LL, Turan M, Duan Xp XP, Kleinerman ES (2002) Eradication of osteosarcoma lung metastasis using intranasal gemcitabine. Anticancer Drugs 13(2):155–161

    Article  PubMed  CAS  Google Scholar 

  • Khanna C, Prehn J, Yeung C, Caylor J, Tsokos M, Helman L (2000) An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. Clin Exp Metastasis 18(3):261–271

    Article  PubMed  CAS  Google Scholar 

  • Kim EM, Sivanandham M, Stavropoulos CI, Wallack MK (2002) Adjuvant effect of a Flt3 ligand (FL) gene-transduced xenogeneic cell line in a murine colon cancer model. J Surg Res 108(1):148–156

    Article  PubMed  CAS  Google Scholar 

  • Lind M, Eriksen EF, Bunger C (1996) Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. Bone 18(1):53–57

    Article  PubMed  CAS  Google Scholar 

  • Link MP, Goorin AM, Miser AW et al (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314(25):1600–1606

    Article  PubMed  CAS  Google Scholar 

  • Luu HH, Kang Q, Park JK, Si W, Luo Q, Jiang W, Yin H, Montag AG, Simon MA, Peabody TD, Haydon RC, Rinker-Schaeffer CW, He TC (2005) An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis. Clin Exp Metastasis 22(4):319–329

    Article  PubMed  Google Scholar 

  • Manara MC, Baldini N, Serra M, Lollini PL, De Giovanni C, Vaccari M, Argnani A, Benini S, Maurici D, Picci P, Scotlandi K (2000) Reversal of malignant phenotype in human osteosarcoma cells transduced with the alkaline phosphatase gene. Bone 26(3):215–220

    Article  PubMed  CAS  Google Scholar 

  • Mankin HJ, Hornicek FJ, Rosenberg AE et al (2004) Survival data for 648 patients with osteosarcoma treated at one institution. Clin Orthop 429:286–291

    Article  PubMed  Google Scholar 

  • McAllister RM, Gardner MB, Greene AE, Bradt C, Nichols WW, Landing BH (1971) Cultivation in vitro of cells from a human osteosarcoma. Cancer 27:397–402

    Article  PubMed  CAS  Google Scholar 

  • McAllister RM, Nelson-Rees WA, Peer M, Laug WE, Isaacs H Jr, Gilden RV, Rongey RW, Gardner MB (1975) Childhood sarcomas and lymphomas. Characterization of new cell lines and search for type-C virus. Cancer 36(5):1804–1814

    Article  PubMed  CAS  Google Scholar 

  • McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M (2002) Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Clin Cancer Res 8(11):3584–3591

    PubMed  CAS  Google Scholar 

  • McGary EC, Heimberger A, Mills L, Weber K, Thomas GW, Shtivelband M, Lev DC, Bar-Eli M (2003) A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo. Clin Cancer Res 9(17):6560–6566

    PubMed  CAS  Google Scholar 

  • Mirandola P, Sponzilli I, Gobbi G, Marmiroli S, Rinaldi L, Binazzi R, Piccari GG, Ramazzotti G, Gaboardi GC, Cocco L, Vitale M (2006) Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins. Int J Oncol 28(1):127–133

    PubMed  CAS  Google Scholar 

  • Morin KW, Duan W, Knaus EE, McEwan AJ, Wiebe LI (2005) A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase: studies with radiolabeled (E)-5-(2-iodovinyl)-2′-fluoro-2′-deoxyuridine. Nucl Med Biol 32(5):459–464

    Article  PubMed  CAS  Google Scholar 

  • Navaraj A, Mori T, El-Deiry WS (2005) Cooperation between BRCA1 and p53 in repair of cyclobutane pyrimidine dimers. Cancer Biol Ther 4(12):1409–1414

    Article  PubMed  CAS  Google Scholar 

  • Orimo H, Shimada T (2005) Regulation of the human tissue-nonspecific alkaline phosphatase gene expression by all-trans-retinoic acid in SaOS-2 osteosarcoma cell line. Bone 36(5):866–876

    Article  PubMed  CAS  Google Scholar 

  • Ponten J, Saksela E (1967) Two established in vitro cell lines from human mesenchymal tumours. Int J Cancer 2:434–447

    PubMed  CAS  Google Scholar 

  • Rhim JS, Cho HY, Vernon ML, Arnstein P, Huebner RJ, Gilden RV (1975) Characterization of non-producer human cells induced by Kirsten sarcoma virus. Int J Cancer 16(5):840–849

    PubMed  CAS  Google Scholar 

  • Schmidt J, Strauss GP, Schon A, Luz A, Murray AB, Melchiori A, Aresu O, Erfle V (1988) Establishment and characterisation of osteogenic cell lines from a spontaneous murine osteosarcoma. Differentiation 39(3):151–160

    Article  PubMed  CAS  Google Scholar 

  • Sihn CR, Suh EJ, Lee KH, Kim SH (2005) Sec13 induces genomic instability in U2OS cells. Exp Mol Med 37(3):255–260

    PubMed  CAS  Google Scholar 

  • Stiller CA, Craft AW, Corazziari I (2001) Survival of children with bone sarcoma in Europe since 1978: results from the EUROCARE study. Eur J Cancer 37:760–766

    Article  PubMed  CAS  Google Scholar 

  • Whelan JS (1997) Osteosarcoma. Eur J Cancer 33:1611–1618

    Article  PubMed  CAS  Google Scholar 

  • Worth LL, Jia SF, Zhou Z, Chen L, Kleinerman ES (2000) Intranasal therapy with an adenoviral vector containing the murine interleukin-12 gene eradicates osteosarcoma lung metastases. Clin Cancer Res 6(9):3713–3718

    PubMed  CAS  Google Scholar 

  • Yu Y, Harris RI, Yang JL, Anderson HC, Walsh WR (2004) Differential expression of osteogenic factors associated with osteoinductivity of human osteosarcoma cell lines. J Biomed Mater Res A 70(1):122–128

    Article  PubMed  CAS  Google Scholar 

  • Zhou H, Choong PF, McCarthy R, Chou ST, Martin TK, Ng KW (1994) In situ hybridisation to show sequential expression of osteoblast gene markers during bone formation in vivo. J Bone Miner Res 9(9):1489–1499

    Article  PubMed  CAS  Google Scholar 

  • Zhu JJ, Li FB, Zhou JM, Liu ZC, Zhu XF, Liao WM (2005) The tumor suppressor p33ING1b enhances taxol-induced apoptosis by p53-dependent pathway in human osteosarcoma U2OS cells. Cancer Biol Ther 4(1):39–47

    Article  PubMed  Google Scholar 

  • Zhu JJ, Li FB, Zhu XF, Liao WM (2006) The p33(ING1b) tumor suppressor cooperates with p53 to induce apoptosis in response to etoposide in human osteosarcoma cells. Life Sci 78(13):1469–1477

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the generous support of the Australian Orthopaedic Association, Victorian Orthopaedic Research Trust Grant, Cancer Council of Victoria, Faculty of Medicine at the University of Melbourne, the Royal Australasian College of Surgeons, and the National Health and Medical Research Council of Australia (NH&MRC).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Crispin R. Dass.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dass, C.R., Ek, E.T.H. & Choong, P.F.M. Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical relevance and applicability for drug testing . J Cancer Res Clin Oncol 133, 193–198 (2007). https://doi.org/10.1007/s00432-006-0157-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-006-0157-x

Keywords

Navigation