Abstract
The purpose of these studies was to identify some characteristics of metastatic cells and deficiencies of non-metastatic cells in the heterogeneous SN12 human renal cell carcinoma. The SN12 parental line and several isolated variants with different metastatic potential were studied bothin vivo andin vitro. We compared the ability of metastatic and non-metastatic cells to adhere to components of the extracellular matrix or to endothelial cells, to migrate and invade, to form multicell aggregates, to survive in the circulation, and to produce experimental and spontaneous lung metastases. In general, highly metastatic SN12 cells capable of producing spontaneous lung metastases demonstrated invasion through reconstituted basement membranecoated filters; the cells also released diffusible collagenolytic activity into the culture medium that could enhance invasion by otherwise non-invasive and non-metastatic SN12 cells. In addition to enhanced invasion, metastatic cells produced more homotypic aggregation then non-metastatic cells and survived to produce experimental metastasis. Collectively, these data confirm that metastatic cells must complete all steps of the process; in this process, failure to produce metastasis is probably due to one or more deficiencies.
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Ahlering, T. E., Dubeau, L., andJones, P. A., 1987, A newin vivo model to study invasion and metastasis of human bladder carcinoma.Cancer Research,47, 6660–6665.
Albini, A., Iwamoto, Y., Kleinman, H. K., Martin, G. R., Aaronson, S. A., Kozlowski, J. M., andMcEwan, R. N., 1987, A rapidin vitro assay for quantitating the invasive potential of tumor cells.Cancer Research,47, 3239–3245.
Bresalier, R. S., Raper, S. E., Hujanen, E. S., andKim, Y. S., 1987, A new model for human colon cancer metastasis.International Journal of Cancer,39, 625–630.
Clayman, R. V., Figenshau, R. S., andBear, A., 1985, Transplantation of human renal carcinomas into athymic mice.Cancer Research,45, 2650–2653.
Cornil, T., Man, M. S., Fernandez, B., andKerbel, R. S., 1989, Enhanced tumorigenicity, melanogenesis and metastasis of the human malignant melanoma observed after subdermal implantation in nude mice.Journal of the National Cancer Institute,81, 938–944.
Fidler, I. J., 1970, Metastasis. Quantitative analysis of distribution and fate of tumor cell emboli labeled with125I-5-iodo-2′-deoxyuridine.Journal of the National Cancer Institute,45, 773–782.
Fidler, I. J., andKripke, M. L., 1978, Metastasis results from pre-existing variant cells within a malignant tumor.Science,197, 893–895.
Fidler, I. J., 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.
Fidler, I. J., andTalmadge, J. E., 1986, Evidence that intravenously derived murine pulmonary metastases can originate from the expansion of a single tumor cell.Cancer Research,46, 5167–5171.
Fidler, I. J., 1990, Critical factors in the biology of human cancer metastasis. 28th G. H. A. Clowes Memorial Award Lecture.Cancer Research,50, 6130–6138.
Giavazzi, R., Campbell, D. E., Jessup, J. M., Cleary, K., andFidler, I. J., 1986, Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites of nude mice.Cancer Research,46, 1928–1933.
Giavazzi, R., Jessup, J. M., Campbell, D. E., Walker, S. M., andFidler, I. J., 1986, Experimental nude mouse model of human colorectal cancer liver metastasis.Journal of the National Cancer Institute,77, 1303–1308.
Goldrosen, M. H., 1980, Murine colon adenocarcinoma immunobiology of metas.Cancer,45, 1223–1228.
Ibrahiem, E. H. I., Nigam, V. N., Brailovsky, C. A., Madarnas, P., andElhilali, M., 1983, Orthotopic implantation of primary (N-[4-(5-nitro2-furyl)-2-thiazolyl]formamide-induced bladder cancer in bladder submucosa. An animal model for bladder cancer study.Cancer Research,43, 617–622.
Jessup, J. M., Giavazzi, R., Campbell, D., Cleary, K. R., Morikawa, K., Hostetter, R., Atkinson, E. N., andFidler, I. J., 1989, Metastatic potential of human colorectal carcinomas implanted into nude mice. Prediction of clinical outcome in patients operated upon for cure.Cancer Research,49, 6906–6910.
Kajiji, S. M., Meitner, P. A., Bogaars, H. A., Dexter, D. L., Calabresi, P., andTurner, M. D., 1982, Metastasis of a human pancreatic adenocarcinoma (RWP-1) in nude mice.British Journal of Cancer,46, 970–975.
Kerbel, R. S., andMan, M. S., 1984, Single-step selection of unique human melanoma variants displaying unusually aggressive metastatic behavior in nude athymic mice.Invasion and Metastasis,4, 31–43.
Kerbel, R. S., Man, M. S., andDexter, D., 1984, A model of human cancer metastasis. Extensive spontaneous and artificial metastasis of a human pigmented melanoma and derived variant sublines in nude mice.Journal of the National Cancer Institute,72, 93–108.
Kleinman, H. K., McGarvey, M. L., Liotta, L. A., Gehron-Robey, P., Tryggvason, K., andMartin, G. R., 1982, Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from EHS sarcoma.Biochemistry,21, 6188–6193.
Kozlowski, J. M., Fidler, I. J., Campbell, D., Xu, Z., Kaighn, M. E., andHart, I. R., 1984, Metastatic behavior of human tumor cell lines grown in the nude mouse.Cancer Research,44, 3522–3529.
Kozlowski, J. M., Hart, I. R., Fidler, I. J., andHanna, N., 1984, A human melanoma line heterogeneous with respect to metastatic capacity in athymic nude mice.Journal of the National Cancer Institute,72, 913–917.
Levy, J. A., White, A. C., andMcGrath, C. M., 1982, Growth and histology of a human mammary-carcinoma cell line at different sites in the athymic mouse.British Journal of Cancer,45, 375–383.
Liotta, L. A., 1986, Tumor invasion and metastasis—role of the extracellular matrix. Rhoads Memorial Award Lecture.Cancer Research,46, 1–7.
Liotta, L. A., Garbisa, S., andTryggvason, K., 1982, Biochemical mechanisms involved in tumor cell penetration of the basement membrane.Tumor Invasion and Metastasis, edited by L. A. Liotta and I. R. Hart (The Hague: Martinus Nijhoff), pp. 319–334.
Marincola, F. M., Drucker, B. J., Siao, D. Y., Hough, K. L., andHolder, W. D. Jr., 1989, The nude mouse as a model for the study of human pancreatic cancer.Journal of Surgical Research,47, 520–529.
McCarthy, J. B., Palm, S. L., andFurcht, L. T., 1983, Migration of haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin.Journal of Cell Biology,97, 772–777.
McCarthy, J. B., andFurcht, L. T., 1984, Laminin and fibronectin promote the haptotactic migration of B16 mouse melanoma cellsin vitro.Journal of Cell Biology,98, 1474–1480.
McCarthy, J. B., Skubitz, A. P. N., Palm, S. L., andFurcht, L. T., 1988, Metastasis inhibition of different tumor types by purified laminin fragments and a heparin-binding fragment of fibronectin.Journal of the National Cancer Institute,80, 108–115.
Morikawa, K., Walker, S. M., Jessup, J. M., andFidler, I. J., 1988,In vivo selection of highly metastatic cells from surgical specimens of different human colon carcinomas implanted into nude mice.Cancer Research,48, 1943–1948.
Morikawa, K., Walker, S. M., Nakajima, M., Pathak, S., Jessup, J. M., andFidler, I. J., 1988, Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice.Cancer Research,48, 6863–6871.
Naito, S., Von Eschenbach, A. C., andFidler, I. J., 1987, Different growth pattern and biologic behavior of human and renal cell carcinoma implanted into different organs of nude mice.Journal of the National Cancer Institute,78, 377–385.
Naito, S., Von Eschenbach, A. C., Giavazzi, R., andFidler, I. J., 1986, Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice.Cancer Research,46, 4109–4115.
Naito, S., Walker, S. M., Von Eschenbach, A. C., andFidler, I. J., 1988, Evidence for metastatic heterogeneity of a human renal cell carcinoma.Anticancer Research,8, 1163–1168.
Naito, S., Walker, S. M., andFidler, I. J., 1989,In vivo selection of human carcinoma cells with high metastatic potential in nude mice.Clinical and Experimental Metastasis,7, 381–389.
Nakajima, M., Morikawa, K., Fabra, A., Bucana, C. D., andFidler, I. J., 1990, Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells.Journal of the National Cancer Institute,82, 1890–1898.
Nicolson, G. L., andPoste, G., 1982, Tumor cell diversity and host responses in cancer metastasis. I. Properties of the metastatic cell.Current Problems in Cancer,6, 4–83.
Nicolson, G. L., Nakajima, M., andIrimura, T., 1985, Invasion of vascular endothelium and organ tissuein vitro by B16 melanoma variants.Mechanisms of Metastasis: Potential Therapeutic Implications, edited by K. V. Honn, W. E. Powers and B. F. Sloane (The Hague: Martinus Nijhoff), pp. 275–297.
Nicolson, G. L., 1988, Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites.Biochimica et Biophysica Acta,948, 175–224.
Pollack, V. A., andFidler, I. J., 1982, Use of young nude mice for selection of subpopulations of cells with increased metastatic potential from nonsyngeneic neoplasms.Journal of the National Cancer Institute,69, 137–141.
Poste, G., andFidler, I. J., 1979, The pathogenesis of cancer metastasis.Nature,283, 139–146.
Poste, G., 1982, Experimental systems for analysis of the malignant phenotype.Cancer and Metastasis Reviews,1, 141–199.
Price, J. E., Aukerman, S. L., andFidler, I. J., 1986, Evidence that the process of murine melanoma metastasis is sequential and selective and contains stochastic elements.Cancer Research,46, 5172–5178.
Price, J. E., Polyzos, A., Zhang, R. D., andDaniels, L. M., 1990, Tumorigeni-city and metastasis of human breast carcinoma cell lines in nude mice.Cancer Research,50, 717–721.
Saiki, I., Iida, J., Murata, J., Ogawa, R., Nichi, N., Sugimura, K., Tokura, S., andAzuma, I., 1989, Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequence of cell-adhesive molecules.Cancer Research,49, 3815–3822.
Saiki, I., Murata, J., Watanabe, K., Fujii, H., Abe, F., andAzuma, I., 1989, Inhibition of tumor cell invasion by Ubenimex (Bestatin)in vitro.Japanese Journal of Cancer Research,80, 873–878.
Saiki, I., Murata, J., Nakajima, M., Tokura, S., andAzuma, I.; 1991, Inhibition of sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells.Cancer Research,50, 3631–3637.
Shafie, S. M., andLiotta, L. A., 1980, Formation of metastasis by human breast carcinoma cells (MCF-7) in nude mice.Cancer Letters,11, 81–87.
Sordat, B. C. M., Ueyama, Y., andFogh, J., 1982, Metastasis of tumor xenografts in the nude mouse.The Nude Mouse in Experimental and Clinical Research, Vol. 2, edited by J. Fogh and B. C. Giovanella (New York: Academic Press), pp. 95–147.
Sordat, B., andWang, W. R., 1984, Human colorectal tumor xenografts in nude mice. Expression of malignancy.Behring Institute Mitt.,74, 291–300.
Tan, M. H., andChu, T. M., 1985, Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (ASPC-1) implanted orthotopically into nude mice.Tumour Biology,6, 89–98.
Terranova, V. P., Hujanen, E. S., andMartin, G. R., 1986, Basement membrane and the invasive activity of metastatic tumor cells.Journal of the National Cancer Institute,77, 311–316.
Updyke, T. V., andNicolson, G. L., 1986, Malignant melanoma cell lines selectedin vitro for increased homotypic adhesion properties have increased experimental metastatic potential.Clinical and Experimental Metastasis,4, 273–284.
Vezeridis, M. P., Turner, M. D., Kajiji, S. M., Yankee, R. A., andMeither, P. A., 1985, Metastasis of human pancreatic cancer (HPC) to liver in nude mice.Proceedings of the American Association for Cancer Research,26, 53.
Vezeridis, M. P., Doremus, C. M., Tobbetts, L. M., Tzanakakis, G., andJackson, B. T., 1989, Invasion and metastasis following orthotopic transplantation of human pancreatic cancer in the nude mouse.Journal of Surgical Oncology,40, 261–265.
Weiss, L., 1985,Principles of Metastasis (Orlando: Academic Press).
Weiss, L., 1986, Metastatic inefficiency. Causes and consequences.Cancer Reviews,3, 1–24.
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Saiki, I., Naito, S., Yoneda, J. et al. Characterization of the invasive and metastatic phenotype in human renal cell carcinoma. Clin Exp Metast 9, 551–566 (1991). https://doi.org/10.1007/BF01768583
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DOI: https://doi.org/10.1007/BF01768583