Abstract
We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(g13), del(7)(q21.2) and inv(11)(pl3q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of β1-integrin of OCUM-2MD3 cells was higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-β1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. β1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.
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References
Tahara E, 1990, Growth factors and oncogenes in human gastrointestinal carcinomas. J Cancer Res Clin Oncol, 116, 121–31.
Kiyasu Y, Kaneshima S and Koga S, 1981, Morphogenesis of peritoneal metastasis in human gastric cancer. Cancer Res, 41, 1236–9.
Yanagihara K, Seyama T, Tsumuraya M, Kamada N and Yokoro K, 1991, Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogenes. Cancer Res, 51, 381–6.
Yanagihara K, Kamada N, Tsumuraya M and Amano F, 1993, Establishment and characterization of a human gastric scirrhous carcinoma cell line in serum-free chemically defined medium. Int J Cancer, 54, 200–7.
Sekiguchi M, Sakakibara K and Fujii G, 1978, Establishment of cultured cell lines from a human gastric carcinoma. Jpn J Exp Med, 48, 61–9.
Terashima M, Ikeda K, Maeawa C, et al. 1991, Establishment of an α-fetoprotein-producing gastric cancer cell line in serum-free media. Jpn J Cancer Res, 82, 883–5.
Altorki N, Schwartz GK, Blundell M, Davis BM, Kelsen DP and Albino AP, 1993, Characterization of cell lines established from human gastric-esophageal adenocarcinomas—biologic phenotype and invasion potential. Cancer, 72, 649–57.
Stephenson RA, Dinney CPN, Gohji K, Ordonez NG, Killion JJ and Fidler IJ, 1992, Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst, 84, 951–7.
Manzotti C, Audisio RA and Pratesi G, 1993, Importance of orthotopic implantation for human tumors as model system: relevance to metastasis and invasion. Clin Exp Metastasis, 11, 5–14.
Fidler IJ, 1991, Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of cancer metastasis. Cancer Metastasis Rev, 10, 229–43.
Fidler IJ, Naito S and Pathak S, 1990, Orthotopic implantation is essential for the selection, growth, and metastasis of human renal cell cancer in nude mice. Cancer Metastasis Rev, 9, 149–65.
Furukawa T, Fu X, Kubota T, Watanabe M, Kitajima M and Hoffman MR, 1993, Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. Cancer Res, 53, 1204–8.
Yashiro M, Chung YS and Sowa M, 1994, Role of orthotopic fibroblasts in the development of scirrhous gastric carcinoma. Jpn J Cancer Res, 85, 883–6.
Seabright M, 1971, A rapid banding technique for human chromosomes. Lancet, 2, 971–2.
Sambrook J, Fritch EF and Maniatis T, 1989, Molecular Cloning. A Laboratory Manual, Vol. 2. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press, pp. 9.16–9.19.
Southern EM, 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Molec Biol, 98, 503–17.
Takeichi M, 1991, The cadherins: cell-cell adhesion molecules controlling animal morphogenetic regulator. Science, 251, 1451–5.
Albini A, Iwamoto Y, Kleiman HK, et al. 1987, A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res, 47, 3239–45.
Liotta LA, Rao CN and Wewer UM, 1986, Biochemical interactions of tumor cells with the basement membrane. Ann Rev Biochem, 55, 1037–57.
Hart IR, 1982, ‘Seed and soil’ revisited; mechanisms of site-specific metastasis. Cancer Metastasis Rev, 1, 17–28.
Filler IJ, 1990, Critical factors in the biology of human cancer metastasis. Twenty-eight G. H. A. Clowes Memorial Award lecture. Cancer Res, 50, 6130–8.
Kuniyasu H, Yasui W, Yokozaki H, et al. 1994, Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas. Int J Cancer, 59, 597–600.
Nakatani H, Sakamoto H, Yoshida T, et al. 1990, Isolation of an amplified DNA sequence in stomach cancer. Jpn J Cancer Res, 81, 707–10.
Hattori Y, Odagiri, H, Nakatani H, et al. 1990, K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes. Proc Natl Acad Sci, USA, 87, 5983–7.
Takeichi M, 1977, Functional correlation between cell adhesive properties and some cell surface proteins. J Cell Biol, 75, 464–74.
Behrens J, Mareel MM, Van Roy FM and Walter B, 1989, Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol, 108, 2435–47.
Shimoyama Y and Hirohashi S, 1991, Expression of E- and P-cadherin in gastric carcinomas. Cancer Res, 51, 2185–92.
Hagiwara A, Takahashi T, Sawai K, et al. 1993, Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice. Cancer Res, 53, 687–92.
Ankrapp DP and Bevan DR, 1993, Insulin-like growth factor-I and human lung fibroblast-derived insulinlike growth factor-I stimulate the proliferation of human lung carcinoma cells in vitro. Cancer Res, 53, 3399–404.
Lawrence DA, Pircher R, Kryceve-Martinerie C and Jullien P, 1984, Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol, 121, 184–8.
Picard O, Rolland Y and Poupon MF, 1986, Fibroblastdependent tumorigenicity of cells in nude mice: implication for implantation of metastasis. Cancer Res, 46, 3290–4.
Sirasuma K, Morioka S, Watatani K, et al. 1988, Growth inhibition and differentiation of human salivary adenocarcinoma cells by medium conditioned with normal human fibroblasts. Cancer Res, 48, 2819–24.
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Yashiro, M., Chung, YS., Nishimura, S. et al. Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. Clin Exp Metast 14, 43–54 (1996). https://doi.org/10.1007/BF00157685
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DOI: https://doi.org/10.1007/BF00157685