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. 1996 Mar;122(3):154–160. doi: 10.1007/BF01366955

Spontaneous lung metastases in a human lung tumor xenograft: A new experimental model

Cecilia Corti 1, Graziella Pratesi 1,✉, Michelandrea De Cesare 1, Rita Pellegrini 1, Roberto Giardini 2, Rosanna Supino 1, Franco Zunino 1
PMCID: PMC12201733  PMID: 8601563

Abstract

The cell line NIH-H460, derived from a human large-cell carcinoma of the lung, became metastatic in the lung of athymic mice after s.c. injection. Using serial s.c. passages of the lung metastasis, a cell line was selected, H460M, which was characterized by an increased metastatic potential compared to the parental cells after s.c. (spontaneous metastases) or i.v. injection (experimental metastases). For the high frequency of lung metastases in the mouse and the short time required to develop metastatic foci, the H460M cells transplanted in nude mice represent a unique preclinical model for biological and therapeutic studies. The paper describes the growth and some biological properties (invasion and migration capability, membrane profile) of this experimental in vivo model.

Key words: Human tumor xenograft, Spontaneous metastasis, Lung tumor

Footnotes

This work was supported in part by Consiglio Nazionale delle Ricerche, Progetto Finalizzato ACRO and by Associazione Italiana per la Ricerca sul Cancro

References

  1. Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368–1383 [DOI] [PubMed] [Google Scholar]
  2. Bottini C, Miotti S, Fiorucci S, Facheris P, Ménard S, Colnaghi MI (1993) Polarization of the α6β4 integrin in ovarian carcinomas. Int J Cancer 54:261–267 [DOI] [PubMed] [Google Scholar]
  3. Brower M, Carney DN, Oie HK, Gazdar AF, Minna JD (1986) Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium. Cancer Res 46:798–806 [PubMed] [Google Scholar]
  4. Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45:2913–2923 [PubMed] [Google Scholar]
  5. 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 [DOI] [PubMed] [Google Scholar]
  6. Geran RI, Greenberg NH, Macdonald MM, Schumacher AM, Abbott BJ (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 3:1–88 [Google Scholar]
  7. Houghton JA, Houghton PJ (1987) The suitability and use of human tumor xenografts. In: Kallman RF (ed) Rodent tumor models in experimental cancer therapy. Pergamon, New York, pp 199–204 [Google Scholar]
  8. Lin W, Pretlow TP, Pretlow II TG, Culp LA (1990) BacteriallacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. Cancer Res 50: 2808–2817 [PubMed] [Google Scholar]
  9. Manzotti C, Audisio RA, Pratesi G (1993) Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasion. Clin Exp Metastasis 11:5–14 [DOI] [PubMed] [Google Scholar]
  10. Macdonald NJ, Steeg PS (1993) Molecular basis of tumour metastasis. Cancer Surv 16:175–199 [PubMed] [Google Scholar]
  11. Martignone S, Pellegrini R, Villa E, Tandon NN, Mastroianni A, Tagliabue E, Ménard S, Colnaghi MI (1992) Characterization of two monoclonal antibodies directed against the 67 kDa high affinity laminin receptor and application for the study of breast carcinoma progression. Clin Exp Metastasis 10:379–386 [DOI] [PubMed] [Google Scholar]
  12. McLemore TL, Blacker PC, Gregg M, Jessee SE, Alley MC, Abbott BJ, Shoemaker RH, Litterst CL, Hubbard WC, Brennan RH, Fine DL, Eggleston JC, Mayo JG, Boyd MR (1987) Intrabronchial implantation. A method for the orthotopic propagation of human lung tumors in athymic nude mice. Chest 91:5S-8S [Google Scholar]
  13. Ménard S, Tagliabue E, Canevari S, Fossati G, Colnaghi MI (1983) Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res 43:1295–1300 [PubMed] [Google Scholar]
  14. Mulvin DW, Howard RB, Mitchell DH, Noker PE, Kruse CA, Chu HD, Bunn PA, Johnston MR (1992) Secondary screening system for preclinical testing of human lung cancer therapies. JNCI 84:31–37 [DOI] [PubMed] [Google Scholar]
  15. Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, Powell J (eds) (1992) Cancer incidence in five continents, Vol 6. IARC Sci Publ No. 120, Lyon
  16. Pellegrini R, Bazzini P, Tosi E, Tagliabue E, Conforti G, Dejana E, Ménard S, Colnaghi MI (1992) Production and characterization of two monoclonal antibodies directed against the integrinβ1 chain. Tumori 78:1–4 [DOI] [PubMed] [Google Scholar]
  17. Pratesi G, Manzotti C, Tortoreto M, Prosperi E, Zunino F (1989) Effects of 5FU and cis-DDP combination on human colorectal tumor xenografts. Tumori 75:60–65 [DOI] [PubMed] [Google Scholar]
  18. Pratesi G, Audisio RA (1992) Tumori umani come modelli sperimentali. Argomenti Oncol 13:1–12 [Google Scholar]
  19. Sharkey FE, Fogh J (1984) Considerations on the use of nude mice for cancer research. Cancer Metastasis Rev 3:341–360 [DOI] [PubMed] [Google Scholar]
  20. Sharkey FE, Fogh JM, Hajdu SI, Fitzgerald PJ, Fogh J (1978) Experience in surgical pathology with human tumor growth in the nude mouse. In: Fogh J, Giovanella BC (eds) The nude mouse in experimental and clinical research. Academic Press, New York pp 187–214 [Google Scholar]
  21. Steel GG (1987) How well do xenografts maintain the therapeutic response characteristics of the source tumor in the donor patient? In: Kallman RF (ed) Rodent tumor models in experimental cancer therapy. Pergamon Press, New York, pp 205–208 [Google Scholar]
  22. Supino R, Mapelli E, Sanfilippo O, Silvestro L (1992) Biological and enzymatic features of human melanoma clones with different invasive potential. Melanoma Res 2:377–384 [DOI] [PubMed] [Google Scholar]
  23. Varki NM, Roome L, Sparkes RS, Miller JE (1987) Microscopic metastasis of a human lung carcinoma cell line in athymic nude mice: isolation of a metastatic variant. Int J Cancer 40:46–52 [DOI] [PubMed] [Google Scholar]
  24. Weinberg RA (1989) Oncogenes, anti-oncogenes and the molecular bases of multistep carcinogenesis. Cancer Res 49:3713–3721 [PubMed] [Google Scholar]
  25. Yu D, Wang S-S, Dulski KM, Tsai C-M, Nicolson GL, Hung M-C (1994)c-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res 54:3260–3266 [PubMed] [Google Scholar]

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