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.
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Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368–1383
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
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
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
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
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
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
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
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
Macdonald NJ, Steeg PS (1993) Molecular basis of tumour metastasis. Cancer Surv 16:175–199
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
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
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
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
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
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 integrinβ 1 chain. Tumori 78:1–4
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
Pratesi G, Audisio RA (1992) Tumori umani come modelli sperimentali. Argomenti Oncol 13:1–12
Sharkey FE, Fogh J (1984) Considerations on the use of nude mice for cancer research. Cancer Metastasis Rev 3:341–360
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
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
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
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
Weinberg RA (1989) Oncogenes, anti-oncogenes and the molecular bases of multistep carcinogenesis. Cancer Res 49:3713–3721
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
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This work was supported in part by Consiglio Nazionale delle Ricerche, Progetto Finalizzato ACRO and by Associazione Italiana per la Ricerca sul Cancro
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Corti, C., Pratesi, G., De Cesare, M. et al. Spontaneous lung metastases in a human lung tumor xenograft: A new experimental model. J Cancer Res Clin Oncol 122, 154–160 (1996). https://doi.org/10.1007/BF01366955
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DOI: https://doi.org/10.1007/BF01366955