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Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors

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The growth and metastatic behavior of three human tumor cell lines and a human colon carcinoma previously passagedin vivo were compared between nude mice and scid mice after xenotransplantation. The three human tumor lines included a bladder carcinoma (T24B), a melanoma (RPMI 7931) and alacZ gene-transduced breast cancer (MDA-MB-435 BAG). ThelacZ gene codes for β-galactosidase, which can be stained blue with chromogenic substrate X-gal, thus allowing the highly sensitive detection and quantitative examination of human cancer metastasis in host mice. Adult (7–14 weeks) NMRI nude and C.B-17 SCID mice were inoculated with 0.5–5 × 106 tumor cells s.c. Comparable take rate, latent period and growth rate of implanted tumors were observed in nude and scid mice for each of the cell lines tested. At the time of autopsy, which varied from 6 to 11 weeks after inoculation, a significantly higher incidence of spontaneous lung metastasis was discovered in scid mice (96%) than in age-matched nude mice (27%, totalP < 0.001).In vitro assays for NK cell-mediated cytotoxicity revealed no significant differences between the two strains of mice. Our results suggest that nude and scid mice are equally suitable for propagating human tumors. However, the metastatic capacity of human tumor cells appears to be better expressed in scid mice. Scid mice may therefore provide an advantageous model for the study of human tumor metastasis.

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References

  1. Fogh J, Fogh JM and Orfeo T, 1977, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice.Journal of the National Cancer Institute,59, 221–225.

    Google Scholar 

  2. Giovanella BC, Stehlin JS, Williams LJ Jr, Lee SS and Shepard RC, 1978, Hetero-transplantation of human cancers into nude mice: a model system for human cancer chemotherapy.Cancer,42, 2269–2281.

    Google Scholar 

  3. Sharkey FE and Fogh J, 1979, Metastasis of human tumors in athymic nude mice.International Journal of Cancer,24, 733–738.

    Google Scholar 

  4. Sordat BCM, Ueyama Y and Fogh J, Metastasis of tumors xenografted in the nude mouse. In: Fogh J and Giovanella BC, eds.The Nude Mouse in Experimental and Clinical Research, vol. 2. New York: Academic Press, 1982, pp. 95–147.

    Google Scholar 

  5. Hanna N and Fidler IJ, 1981, Expression of metastatic potential of allogenic and xenogeneic neoplasms in young nude mice.Cancer Research,41, 438–444.

    Google Scholar 

  6. Kozlowski JM, Fidler IJ, Campbell D, Xu ZL, Kaighn ME and Hart IR, 1984, Metastatic behavior of human tumor cell lines grown in nude mouse.Cancer Research,44, 3522–3529.

    Google Scholar 

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

    Google Scholar 

  8. Hanna N, Davis TW and Fidler IJ, 1982, Environmental and genetic factors determine the level of NK activity of nude mice and affect their suitability as models for experimental metastasis.International Journal of Cancer,30, 371–376.

    Google Scholar 

  9. Doré JF, Bailly M and Bertrand S, 1987, Metastasis of human tumors in experimental animals.Anticancer Research,7, 997–1004.

    Google Scholar 

  10. Fidler IJ, Pollack VA and Hanna N, The use of nude mice for studies of cancer metastasis. In: Sordat B, ed.Immune-Deficient Animals. 4th Inter national Workshop on Immune-Deficient Animals in Experimental Research, Chexbres 1982. Basel: Karger, 1984, pp. 328–338.

    Google Scholar 

  11. Hanna N, 1980, Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity.International Journal of Cancer,26, 675–680.

    Google Scholar 

  12. Clark EA, Schultz LD and Pollack SB, 1981, Mutations in mice that influence natural killer (NK) cell activity.Immunogenetics,12, 601–613.

    Google Scholar 

  13. Fodstad Ø, Hansen CT, Cannon GB, Statham CN, Lichtenstein GR and Boyd MR, 1984, Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects.Cancer Research,44, 4403–4408.

    Google Scholar 

  14. Naito S, Giavazzi R, Walker SM, Itoh K, Mayo J and Fidler IJ, 1987, Growth and metastatic behaviour of human tumor cells implanted into nude and beige nude mice.Clinical and Experimental Metastasis,5, 135–146.

    Google Scholar 

  15. Zietman AL, Sugiyama E, Ramsay JR,et al., 1991, A comparative study on the xenotransplantability of human solid tumors into mice with different immune deficiencies.International Journal of Cancer,47, 755–759.

    Google Scholar 

  16. Schuler W, Weiler IJ, Schuler A,et al., 1986, Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency.Cell,46, 963–972.

    Google Scholar 

  17. Bosma GC, Custer RP and Bosma JM, 1983, A severe combined immunodeficiency mutation in the mouse.Nature,301, 527–530.

    Google Scholar 

  18. Mosier DE, Gulizia RJ, Baird SM and Wilson DB, 1988, Transfer of a functional human immune system to mice with severe combined immunodeficiency.Nature,335, 256–259.

    Google Scholar 

  19. Phillips RA, Jewett MAS and Gallic BL, 1989, Growth of human tumors in immune-deficient scid mice and nude mice.Current Topics in Microbiology and Immunology,152, 258–263.

    Google Scholar 

  20. Ghetie MA, Richardson J, Tucker T, Jones D, Uhr JW and Vitetta ES, 1990, Disseminated or localized growth of a human B-cell tumor (Daudi) in scid mice.International Journal of Cancer,45, 481–485.

    Google Scholar 

  21. Reddy S, Piccione D, Takita H and Bankert RB, 1987, Human lung tumor growth established in the lung and subcutaneous tissue of mice with severe combined immunodeficiency.Cancer Research,47, 2456–2460.

    Google Scholar 

  22. Hill LL, Korngold R, Jaworsky C, Murphy G, McCue P and Berd D, 1991, Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency.Cancer Research,51, 4937–4041.

    Google Scholar 

  23. Nomura T, Takahama Y, Hongyo T,et al., 1990, Acid (severe combined immunodeficiency) mice as a new system to investigate metastasis of human tumors.Journal of Radiation Research Tokyo,31, 288–292.

    Google Scholar 

  24. Kieler J, Moore J, Biezowa B and Radzikowski C, 1971, Comparative studies of the cytologic and metabolic characteristics of C3H mouse cells during ‘spontaneous’ alteration and neoplastic conversionin vitro.Acta Pathologica Microbiologica Scandinavica,79, 529–544.

    Google Scholar 

  25. Gerner RE, Kitamura H and Moore GE, 1975, Studies of tumor cell lines derived from patients with malignant melanoma.Oncology,31, 31–43.

    Google Scholar 

  26. Brünner N, Thompson EW, Spang-Thomsen M, Rygaard J, Danø K and Zwiebel JA, 1991,LacZ transduced human tumor xenografts as anin vivo model for the study of invasion and metastasis. (submitted toEuropean Journal of Cancer).

  27. Brinkley BR, Beall PT, Wible LJ, Mace ML, Turner DS and Cailleau RM, 1980, Variations in cell form and cytoskeleton in human breast carcinoma cellsin vitro.Cancer Research,40, 3118–3129.

    Google Scholar 

  28. Lin WC, Pretlow TP, Pretlow TG II and Culp LA, 1990, BacterialLacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression.Cancer Research,50, 2808–2817.

    Google Scholar 

  29. Nolan GP, Fiering S, Nicolas J-F and Herzenberg LA, 1988, Fluorescence-activated cell analysis and sorting of viable mammalian cells based on β-Dgalactosidase activity after transduction of Escherichiacoli lacZ.Proceedings of the National Academy of Sciences USA,85, 2603–2607.

    Google Scholar 

  30. Rygaard K and Spang-Thomsen M, Growth-a computer program for determination of mean growth curves and calculation of response of therapy to solid tumor xenografts. In: Wu B-q and Zhang J, eds.Immune-Deficient Animals in Experimental Medicine. 6th International Workshop on ImmunoDeficient Animals, Beijing 1988, Basel: Karger, 1989, pp. 301–306.

    Google Scholar 

  31. Budzynski W, Chirigos M and Gruys E, 1987, Augmentation of natural cell activity in tumor-bearing and normal mice by MVE-2.Cancer Immunology and Immunotherapy,24, 253–258.

    Google Scholar 

  32. Visfeldt J, Povlsen CO and Rygaard J, 1972, Chromosome analysis of human tumors following heterotransplantation to the mouse mutant nude.Acta Pathologica Microbiologica Scandinavica, Section A,80, 169–176.

    Google Scholar 

  33. Harrison CJ, Diagnosis of malignancy from chromosome preparations. In: Rooney DE and Czepulkowski BH, eds.Human Cytogenetics, a Practical Approach. Oxford: IRL Press, 1986, pp. 144–150.

    Google Scholar 

  34. Benn PA and Perle MA, Chromosome staining and banding techniques. In: Rooney DE and Czepulkowski BH, eds.Human Cytogenetics, a Practical Approach. Oxford: IRL Press, 1986 pp. 57–84.

    Google Scholar 

  35. Kyriazis AP, Dipersio L, Michael GJ, Pesce AJ and Stinnett JD, 1978, Growth patterns and metastatic behavior of human tumors growing in athymic mice.Cancer Research,38, 3186–3190.

    Google Scholar 

  36. Herberman RB, Nunn ME and Lavrin DH, 1975, Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity.International Journal of Cancer,16, 216–229.

    Google Scholar 

  37. Fidler IJ, 1974, Inhibition of pulmonary metastasis by intravenous injection of specifically activated macrophages.Cancer Research,34, 1074–1078.

    Google Scholar 

  38. Loveless SE and Heppner GH, 1983, Tumor-associated macrophages of mouse mammary tumors. I. Differential cytotoxicity of macrophages from meta static and nonmetastatic tumor.Journal of Immunology,131, 2074–2078.

    Google Scholar 

  39. Martin SE and Martin WJ, 1975, Antitumor antibodies in normal mouse sera.International Journal of Cancer,15, 658–664.

    Google Scholar 

  40. Hanna N and Fidler IJ, 1981, Relationship between metastatic potential and resistance to natural killer cell-mediated cytotoxicity in the three murine tumor systems.Journal of the National Cancer Institute,66, 1183–1189.

    Google Scholar 

  41. Dorshkind K, Pollack SB, Bosma MJ and Phillips RA, 1985, Natural killer (NK) cells are present in mice with severe combined immunodeficiency (scid).Journal of Immunology,134, 3798–3801.

    Google Scholar 

  42. Povlsen CO, Fialkow PJ, Klein E, Klein G, Rygaard J and Wiener F, 1973, Growth and antigenic properties of a biopsy-derived Burkitt's lymphoma in thymusless (nude) mice.International Journal of Cancer,11, 30–39.

    Google Scholar 

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Authors and Affiliations

  1. Bartholin Instituttet, Kommunehospitalet, 1399, Copenhagen

    Xiong Xie, Jens Albrectsen & Jørgen Rygaard

  2. Finsen Laboratory, Strandboulevarden 49, 2100, Copenhagen

    Nils Briinnert

  3. Department of Pathology, Frederiksberg Hospital, 2000, Frederiksberg

    Grethe Jensen

  4. The Royal Danish School of Pharmacy, 2100, Copenhagen, Denmark

    Bente Gotthardsen

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  1. Xiong Xie
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  2. Nils Briinnert
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  4. Jens Albrectsen
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  5. Bente Gotthardsen
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  6. Jørgen Rygaard
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Xie, X., Briinnert, N., Jensen, G. et al. Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors. Clin Exp Metast 10, 201–210 (1992). https://doi.org/10.1007/BF00132752

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  • DOI: https://doi.org/10.1007/BF00132752

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