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. 2006 Jul 17;39(2):248–254. doi: 10.1002/ijc.2910390221

Characterization of an animal model of metastatic colon carcinoma

Damien J Dunnington 1,✉, Charles Buscarino 1, Doris Gennaro 1, Russell Greig 1, George Poste 2
PMCID: PMC7165865  PMID: 3804494

Abstract

Although numerous animal tumor models have been used to study colon carcinoma, few display metastatic properties. We have characterized an animal tumor model that has 3 properties essential for the study of metastasis of colon carcinoma cells: epithelial cell origin; a reproducible pattern of metastatic behavior and the ability to be propagated both in vitro and in vivo to facilitate identification of biochemical correlates of metastasis. The KI2/TR cell line was derived from a transplantable colon carcinoma induced by dimethylhydrazine in the BD‐IX rat strain. Transmission electron microscopy of KI2/TR cells demonstrated junctional complexes, desmosomes and surface microvilli characteristic of gastrointestinal epithelial cells. The epithelial cell origin of KI2/TR was confirmed by demonstrating the presence of keratin, a marker of epithelial cells, but not vimentin, a constituent of mesenchymal cells. Secretion of CEA and Ca19‐9 antigens by KI2/TR cells in vitro was below the sensitivity of the assays (1 ng/ml and 6 U/ml respectively). KI2/TR cells produced tumors following s.c. injection into syngeneic BD‐IX rats, allogeneic RNU/rnuDF rats and xenogeneic CRL:nu/nuBR mice. Macroscopic lung metastases were observed in animals from all 3 groups. Distal lymph node metastases were more frequent in BD‐IX rats than in nude rats or mice. The histological appearances of all tumors and metastases were similar, showing a moderate to poorly differentiated glandular carcinoma. Intrasplenic injections of KI2/TR cells in nude mice resulted in liver colonization. Preferential growth of tumor cells at sites of trauma was also observed. The results show that the KI2/TR system can be used as a model to study metastasis of colon carcinoma cells and may find utility in the testing of chemotherapeutic agents against metastatic lesions.

References

  1. Bennett, D. C. , Peachey, L. A. , Durbin, H. , and Rudland, P. S. , A possible mammary stem cell line. Cell, 13, 283–298 (1978). [DOI] [PubMed] [Google Scholar]
  2. Caignard, A. , Martin, M. S. , Michel, M. F. , and Martin, F. , Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host. Int. J. Cancer, 36, 273–279 (1985). [DOI] [PubMed] [Google Scholar]
  3. Carr, I. , Lymphatic metastasis. Cancer Metastasis Rev., 2, 307–317 (1983). [DOI] [PubMed] [Google Scholar]
  4. Corbett, T. H. , Griswold, D. P. , Robert, B. J. , Peckham, J. C. , and Schabel, F. M. , Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assay with a note on carcinogen structure. Cancer Res., 35, 2434–2439 (1975). [PubMed] [Google Scholar]
  5. Dexter, D. L. , Barbosa, J. A. , and Calabresi, P. , N, N‐dimethylformamide‐induced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells. Cancer Res., 39, 1020–1025 (1979). [PubMed] [Google Scholar]
  6. Drewinko, B. , Yang, L. Y. , Leibovitz, A. , Barlogie, B. , Lutz, D. , Jansson, B. , Stragand, J. J. , and Trujillo, J. M. , Cellular discriminants for a biological classification of human colon carcinoma. Cancer Res., 44, 4241–4253 (1984). [PubMed] [Google Scholar]
  7. Dulbecco, R. , Henahan, M. , Bowman, M. , Okada, S. , Battifora, H. , and Unger, M. , Generation of fibroblast‐like cells from cloned epithelial mammary cells in vitro: a possible new cell type. Proc. nat. Acad. Sci. US, 78, 2345–2349 (1981). [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edynak, E. M. , An immunologic rationale for suture line recurrence in carcinoma of the colon. J. surg. Res., 16, 235–240 (1974). [DOI] [PubMed] [Google Scholar]
  9. Franke, W. W. , Schmid, E. , Winter, S. , Osborn, M. , and Weber, K. , Widespread occurrence of intermediate‐sized filaments of the vimentin type in cultured cells from diverse vertebrates. Exp. Cell Res., 123, 25–46 (1979). [DOI] [PubMed] [Google Scholar]
  10. Gorelik, E. , Wiltrout, R. H. , Ukumura, K. , Habu, S. , and Herberman, R. B. , Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. Int. J. Cancer, 30, 107–112 (1982). [DOI] [PubMed] [Google Scholar]
  11. Hoover, H. C. , Surdyke, M. G. , Dangel, R. B. , Peters, L. C. , and Hanna, M. G. , Prospectively randomized trial of adjuvant active specific immunotherapy for human colorectal cancer. Cancer, 55, 1236–1243 (1985). [DOI] [PubMed] [Google Scholar]
  12. Koprowski, H. , Herlyn, M. , Steplewski, Z. , and Sears, H. F. , Specific antigen in serum of patients with colon carcinoma. Science, 212, 53–55 (1981). [DOI] [PubMed] [Google Scholar]
  13. Kozlowski, J. M. , Fidler, I. J. , Campbell, D. , Xu, Z. , Kaighn, M. E. , and Hart, I. R. , Metastatic behavior of human cell lines grown in the nude mouse. Cancer Res., 44, 3522–3529 (1984). [PubMed] [Google Scholar]
  14. Lafrentere, R. , and Rosenberg, S. A. , A novel approach to the generation and identification of experimental hepatic metastases in a murine model. J. nat. Cancer Inst., 76, 309–315 (1986). [PubMed] [Google Scholar]
  15. Laurence, D. J. R. , Stevens, U. , Bettelheim, R. , Darcy, D. , Leese, C. , Turberville, C. , Alexander, P. , Johns, E. W. , and Neville, A. M. , Role of plasma carcinoembryonic antigen in diagnosis of gastrointestinal, mammary and bronchial carcinoma. Brit. Med. J., 3, 605–609 (1972). [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Martin, F. , Caignard, A. , Jeannin, J. F. , Leclerc, A. , and Martin, M. S. , Selection by trypsin of two sublines of rat colon cancer cells forming progressive or regressive tumors. Int. J. Cancer, 32, 623–627 (1983). [DOI] [PubMed] [Google Scholar]
  17. Martin, M. S. , Bastien, H. , Martin, F. , Michiels, R. , Martin, M. R. , and Justrabo, E. , Transplantation of intestinal carcinoma in inbred rats. Biomedicine, 12, 555–558 (1973). [Google Scholar]
  18. McGrath, C. M. , Cell organization and responsiveness to hormones in vitro: genesis of domes in mammary cultures. Amer. J. Zool., 15, 231–236 (1975). [Google Scholar]
  19. Moll, R. , Franke, W. W. , Schiller, D. L. , Geiger, B. , and Krepler, R. , The catalog of human cytokeratins: patterns of expression in normal epithelial tumors and cultured cells. Cell, 31, 11–24 (1982). [DOI] [PubMed] [Google Scholar]
  20. Pozharisski, K. M. , The significance of nonspecific injury for colon carcinogenesis in rats. Cancer Res., 35, 3824–3830 (1975). [PubMed] [Google Scholar]
  21. Ross, D. S. , Steele, G. , Madara, J. , Lahey, S. J. , Ravikumar, T. S. , Wilson, R. E. , Munroe, A. E. , Wright, D. , and King, V. P. , Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2‐Dimethylhydrazine‐induced bowel cancer. J. nat. Cancer Inst., 73, 731–735 (1984). [PubMed] [Google Scholar]
  22. Sharkey, F. E. , and Fogh, J. , Metastasis of human tumors in athymic nude mice. Int. J. Cancer, 24, 733–738 (1979). [DOI] [PubMed] [Google Scholar]
  23. Sugarbaker, P. H. , MacDonald, J. S. , and Gunderson, L. L. , Colorectal cancer In: DeVita V. T., Hellman S., and Rosenberg S. A. (eds.), Cancer: principles and practice of oncology, pp. 643–723, Lippincott, Philadelphia: (1982). [Google Scholar]
  24. Thombre, P. S. , and Deodhar, S. D. , Inhibition of liver metastases in murine colon adenocarcinoma by liposomes containing human C‐reactive protein or crude lymphokine. Cancer Immunol. Immunother., 16, 145–150 (1984). [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsuruo, T. , Yamori, T. , Naganuma, K. , Tsukagoshi, S. , and Sakurai, Y. , Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma‐26. Cancer Res., 43, 5437–5442 (1983). [PubMed] [Google Scholar]
  26. Weisburger, J. H. , and Fiala, E. S. , Experimental colon carcinogens and their mode of action In: Autrup H. and Williams G. M. (eds.), Experimental colon carcinogenesis, pp. 27–50. CRC Press, Boca Raton: (1983). [Google Scholar]

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