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. 1994 Nov;70(5):804–812. doi: 10.1038/bjc.1994.403

Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern.

E K Rofstad 1
PMCID: PMC2033522  PMID: 7947084

Abstract

Adequate tumour models are a prerequisite in experimental cancer research. The purpose of the present work was to establish and assess the validity of four new orthotopic human melanoma xenograft model systems (A-07, D-12, R-18, U-25). Permanent cell lines were established in monolayer culture from subcutaneous metastases of four different melanoma patients by using an in vivo-in vitro procedure, and cells from these lines were inoculated intradermally in Balb/c nu/nu mice to form tumours. Individual xenografted tumours of the same line differed substantially in growth and pathophysiological parameters, probably as a consequence of differences between inoculation sites in host factors which influence tumour angiogenesis. Nevertheless, xenografted tumours of different lines showed distinctly different biological characteristics. Several biological characteristics of the donor patients' tumours were retained in the xenografted tumours, including angiogenic potential; growth, histopathological and pathophysiological parameters; and sensitivity to radiation, heat and dacarbazine treatment. Moreover, the organ-specific metastatic pattern of the xenografted tumours reflected the pattern of distant metastases in the donor patients. The organs of preference for distant metastases were lungs (A-07, D-12), lymph nodes (R-18) and brain (U-25). R-18 lymph node metastases and U-25 brain metastases developed in the absence of lung involvement. The four orthotopic human melanoma xenograft model systems show great promise for future studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern.

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Selected References

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  1. Cornil I., Man S., Fernandez B., Kerbel R. S. Enhanced tumorigenicity, melanogenesis, and metastases of a human malignant melanoma after subdermal implantation in nude mice. J Natl Cancer Inst. 1989 Jun 21;81(12):938–944. doi: 10.1093/jnci/81.12.938. [DOI] [PubMed] [Google Scholar]
  2. Courtenay V. D., Mills J. An in vitro colony assay for human tumours grown in immune-suppressed mice and treated in vivo with cytotoxic agents. Br J Cancer. 1978 Feb;37(2):261–268. doi: 10.1038/bjc.1978.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dean P. N., Jett J. H. Mathematical analysis of DNA distributions derived from flow microfluorometry. J Cell Biol. 1974 Feb;60(2):523–527. doi: 10.1083/jcb.60.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Denekamp J. Experimental tumor systems: standardization of endpoints. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1175–1184. doi: 10.1016/0360-3016(79)90637-0. [DOI] [PubMed] [Google Scholar]
  5. Fidler I. J. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1990 Oct 1;50(19):6130–6138. [PubMed] [Google Scholar]
  6. Fidler I. J. Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis. Cancer Metastasis Rev. 1991 Oct;10(3):229–243. doi: 10.1007/BF00050794. [DOI] [PubMed] [Google Scholar]
  7. Folkman J. Tumor angiogenesis. Adv Cancer Res. 1985;43:175–203. doi: 10.1016/s0065-230x(08)60946-x. [DOI] [PubMed] [Google Scholar]
  8. Fu X. Y., Besterman J. M., Monosov A., Hoffman R. M. Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9345–9349. doi: 10.1073/pnas.88.20.9345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hill R. P. Tumor progression: potential role of unstable genomic changes. Cancer Metastasis Rev. 1990 Sep;9(2):137–147. doi: 10.1007/BF00046340. [DOI] [PubMed] [Google Scholar]
  10. Kallman R. F., Brown J. M., Denekamp J., Hill R. P., Kummermehr J. The use of rodent tumors in experimental cancer therapy. Conclusions and recommendations from an international workshop. Cancer Res. 1985 Dec;45(12 Pt 1):6541–6545. [PubMed] [Google Scholar]
  11. Kreisle R. A., Ershler W. B. Investigation of tumor angiogenesis in an id mouse model: role of host-tumor interactions. J Natl Cancer Inst. 1988 Aug 3;80(11):849–854. doi: 10.1093/jnci/80.11.849. [DOI] [PubMed] [Google Scholar]
  12. Nagelhus T. A., Rofstad E. K. Expression of the chondroitin sulphate proteoglycan molecular complex in six human melanoma xenograft lines studied by flow cytometry and immunohistochemistry. Melanoma Res. 1993 Jun;3(3):187–194. doi: 10.1097/00008390-199306000-00007. [DOI] [PubMed] [Google Scholar]
  13. Rofstad E. K. Comparative sensitivity of cells from human tumors and derivative tumor xenografts to radiation and heat treatments. J Natl Cancer Inst. 1992 Oct 7;84(19):1517–1524. doi: 10.1093/jnci/84.19.1517. [DOI] [PubMed] [Google Scholar]
  14. Rofstad E. K., DeMuth P., Fenton B. M., Sutherland R. M. 31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia. Cancer Res. 1988 Oct 1;48(19):5440–5446. [PubMed] [Google Scholar]
  15. Rofstad E. K. Local tumor control following single dose irradiation of human melanoma xenografts: relationship to cellular radiosensitivity and influence of an immune response by the athymic mouse. Cancer Res. 1989 Jun 15;49(12):3163–3167. [PubMed] [Google Scholar]
  16. Rofstad E. K., Pettersen E. O., Lindmo T., Oftebro R. The proliferation kinetics of NHIK 1922 cells in vitro and in solid tumours in athymic mice. Cell Tissue Kinet. 1980 Mar;13(2):163–171. doi: 10.1111/j.1365-2184.1980.tb00459.x. [DOI] [PubMed] [Google Scholar]
  17. Rofstad E. K. Radiation biology of human tumour xenografts. Int J Radiat Biol. 1989 Nov;56(5):573–581. doi: 10.1080/09553008914551761. [DOI] [PubMed] [Google Scholar]
  18. Rofstad E. K. Radiation sensitivity in vitro of primary tumors and metastatic lesions of malignant melanoma. Cancer Res. 1992 Aug 15;52(16):4453–4457. [PubMed] [Google Scholar]
  19. Rofstad E. K., Wahl A., Brustad T. Radiation sensitivity in vitro of cells isolated from human tumor surgical specimens. Cancer Res. 1987 Jan 1;47(1):106–110. [PubMed] [Google Scholar]
  20. Runkel S., Hunter N., Milas L. An intradermal assay for quantification and kinetics studies of tumor angiogenesis in mice. Radiat Res. 1991 May;126(2):237–243. [PubMed] [Google Scholar]
  21. Solesvik O. V., Rofstad E. K., Brustad T. Vascular structure of five human malignant melanomas grown in athymic nude mice. Br J Cancer. 1982 Oct;46(4):557–567. doi: 10.1038/bjc.1982.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Steel G. G., Courtenay V. D., Peckham M. J. The response to chemotherapy of a variety of human tumour xenografts. Br J Cancer. 1983 Jan;47(1):1–13. doi: 10.1038/bjc.1983.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sutherland R. M., Rasey J. S., Hill R. P. Tumor biology. Am J Clin Oncol. 1988 Jun;11(3):253–274. doi: 10.1097/00000421-198806000-00004. [DOI] [PubMed] [Google Scholar]
  24. Vaupel P., Fortmeyer H. P., Runkel S., Kallinowski F. Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res. 1987 Jul 1;47(13):3496–3503. [PubMed] [Google Scholar]
  25. Vaupel P., Kallinowski F., Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989 Dec 1;49(23):6449–6465. [PubMed] [Google Scholar]
  26. Vindeløv L. L., Christensen I. J., Nissen N. I. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry. 1983 Mar;3(5):323–327. doi: 10.1002/cyto.990030503. [DOI] [PubMed] [Google Scholar]

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