Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1987 Feb;24(1):13–18. doi: 10.1007/BF00199827

Human carcinoma cell lines xenografted in athymic mice: biological and antigenic characteristics of an intraabdominal model

Marina Ripamonti 1, Silvana Canevari 1, Sylvie Ménard 1, Delia Mezzanzanica 1, Silvia Miotti 1, Rosaria Orlandi 1, Franco Rilke 2, Elda Tagliabue 1, Maria Ines Colnaghi 1,
PMCID: PMC11038650  PMID: 3545465

Abstract

In order to investigate in vivo clinical applications of murine monoclonal antibodies directed against human ovarian carcinoma a preclinical in vivo model was developed using BALB/c athymic mice. Three human carcinoma cell lines (MCF7, HT29, and SW626) were injected into the peritoneal cavity of pristane-primed animals and the biological and antigenic characteristics of the i.p. grown tumors were studied. The animals were killed when moribund or 6–8 weeks after tumor injection. At autopsy tumor take was observed in 85% of the injected animals, whereas palpable nodules were evident in only 83%. Examination of the peritoneal cavity revealed intraabdominal carcinomatosis with tumor masses varying in size between 0.2 and 0.5 cm in diameter and tumor sheets. The most frequently affected organs were the diaphragm, the liver, and the reproductive system. Ascitic fluid formation was rare and no animal developed tumors outside the peritoneal cavity. To determine whether the in vivo tumors retained the same antigenic characteristics as the in vitro cell lines, four monoclonal antibodies (MBrl, MOv2, MOv8, and MOv15) directed against ovarian carcinoma-associated antigens and two different experimental approaches (immunofluorescence and immunoblotting) were used. Variations at either a quantitative or a qualitative level were observed for some antigens, whereas no evident changes were apparent for others. In particular, the antigens detected by MBr1 and MOv15 on the MCF7 line both maintained high levels of expression and immunoblotting staining pattern, whereas the antigens detected by MOv2 on the HT29 and SW626 lines, although present at a high level, clearly changed their staining pattern. As regards the antigens recognized by MOv8 and MOv15 on the HT29 and SW626 lines, we observed a drastic decrease in the level of their expression and in many cases a drop below the threshold of detectability of the test. The intraabdominal carcinomatosis described partially mimics the growth characteristics of human ovarian cancer and maintains the expression of some antigenic markers associated with epithelial tumors of the ovary and may therefore be useful in devising immunodiagnostic and/or immunotherapeutic strategies for ovarian carcinoma.

Keywords: Ovarian Cancer, Peritoneal Cavity, Ovarian Carcinoma, Ascitic Fluid, Human Ovarian Cancer

References

  • 1.Bast RCJ, Knapp RC. The immunobiology of ovarian carcinoma. In: Griffiths CT, Fuller AF, editors. Gynecologic oncology. Boston: Martinus Nijhoff Publishers; 1983. p. 187. [Google Scholar]
  • 2.Bast RJ, Feeney M, Lazarus H, Nadler L, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331. doi: 10.1172/JCI110380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bast RC, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, Berkolwitz RS, Leavitt T, Griffiths T, Parker L, Zurawski VRJ, Knapp RC. Radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309:883. doi: 10.1056/NEJM198310133091503. [DOI] [PubMed] [Google Scholar]
  • 4.Bhattacharya M, Chatterjee SK, Barlow JJ, Fuji H. Monoclonal antibodies recognizing tumor-associated antigen of human ovarian mucinous cystadenocarcinoma. Cancer Res. 1982;42:1650. [PubMed] [Google Scholar]
  • 5.Bhattacharya M, Chatterjee SK, Barlow JJ. Identification of a human cancer-associated antigen defined with monoclonal antibody. Cancer Res. 1984;44:4528. [PubMed] [Google Scholar]
  • 6.Bhattacharya M, Chatterjee SK, Gangopadhyay A, Barlow JJ. Production and characterization of monoclonal antibody to a 60-kD glycoprotein in ovarian carcinoma. Hybridoma. 1985;4:153. doi: 10.1089/hyb.1985.4.153. [DOI] [PubMed] [Google Scholar]
  • 7.Canevari S, Fossati G, Balsari A, Sonnino S, Colnaghi MI. Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells. Cancer Res. 1983;43:1301. [PubMed] [Google Scholar]
  • 8.Canevari S, Orlandi R, Ripamonti M, Tagliabue E, Aguanno S, Miotti S, Ménard S, Colnaghi MI. Ricin A chain conjugated with monoclonal antibodies selectively killing human carcinoma cells in vitro. J Natl Cancer Inst. 1985;75:831. doi: 10.1093/jnci/75.5.831. [DOI] [PubMed] [Google Scholar]
  • 9.Colnaghi MI, Canevari S, Della Torre G, Mariani-Costantini R, Ménard S, Miotti S, Rilke F. Use of monoclonal antibodies for breast cancer diagnosis and prognosis. In: Ceriani RL, editor. Monoclonal antibodies and breast cancer. Boston: Martinus Nijhoff Publishing; 1985. p. 153. [Google Scholar]
  • 10.Davy M, Mossiage J, Johannessen JV. Heterologous growth of human ovarian cancer. Acta Obstet Gynecol Scand. 1977;56:55. doi: 10.3109/00016347709158340. [DOI] [PubMed] [Google Scholar]
  • 11.Ey PL, Prowse SJ, Jenkin CR. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978;15:429. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  • 12.Giovanella BC, Fogh J. Present and future trends in investigations with the nude mouse as a recipient of human tumor transplants. In: Fogh J, Giovanella BC, editors. The nude mouse in experimental and clinical research. New York: Academic Press; 1978. p. 281. [Google Scholar]
  • 13.Gold DV, Shochat D, Primus FJ, Dexter DL, Calabresi P, Goldenberg DM. Differential expression of tumor-associated antigens in human colon carcinomas xenografted into nude mice. J Natl Cancer Inst. 1983;71:117. [PubMed] [Google Scholar]
  • 14.Hakomori SI, Kannagi R. Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst. 1983;71:231. [PubMed] [Google Scholar]
  • 15.Hamilton TC, Young RC, Louie KG, Behrens BC, McKoy WM, Grotzinger KR, Ozols RF. Characterization of a xenograft model of human ovarian carcinoma which produces ascites and intraabdominal carcinomatosis in mice. Cancer Res. 1984;44:5286. [PubMed] [Google Scholar]
  • 16.IFGO (1976) Annual report on the results of treatment in carcinoma of the uterus, vagina and ovary. Vol 16 [DOI] [PubMed]
  • 17.Johnson VG, Schlom J, Paterson AJ, Bennett J, Magnani JL, Colcher D. Analysis of a human tumor-associated glycoprotein (TAG-72) identified by monoclonal antibody B72.3. Cancer Res. 1986;46:850. [PubMed] [Google Scholar]
  • 18.Klug TL, Salzman S, Quinn A, Melincoff GA, Sedmak DD, Tubbs RR, Zurawski VRJ. Tumorigenicity in athymic mice of the human colon carcinoma cell line SW1116 expressing the tumor-associated antigenic determinant Ca 19-9. Cancer Res. 1984;44:5212. [PubMed] [Google Scholar]
  • 19.Kullander S, Rausing A, Trope C. Human ovarian tumors heterotransplanted to “nude” mice. Obstet Acta Gynecol Scand. 1978;57:1492. doi: 10.3109/00016347809155895. [DOI] [PubMed] [Google Scholar]
  • 20.Leoni F, Miotti S, Canevari S, Sonnino S, Ripamonti M, Colnaghi MI. Carbohydrate epitope defined by an antitumor monoclonal antibody detected on glycoproteins and glycolipid by immunoblotting. Hybridoma. 1986;5:289. doi: 10.1089/hyb.1986.5.289. [DOI] [PubMed] [Google Scholar]
  • 21.Mach JP, Carrel S, Merenda C, Sordat B, Cerottini JC. In vivo localization of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice. Nature. 1974;248:704. doi: 10.1038/248704a0. [DOI] [PubMed] [Google Scholar]
  • 22.Mattes MJ, Cordon-Cardo C, Lewis JLJ, Old LJ, Lloyd KO. Cell surface antigens of human ovarian and endometrial carcinoma defined by mouse monoclonal antibodies. Proc Natl Acad Sci USA. 1984;81:568. doi: 10.1073/pnas.81.2.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Ménard S, Tagliabue E, Canevari S, Fossati G, Colnaghi MI. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res. 1983;43:1295. [PubMed] [Google Scholar]
  • 24.Miotti S, Aguanno S, Canevari S, Diotti A, Orlandi R, Sonnino S, Colnaghi MI. Biochemical analysis of human ovarian cancer-associated antigens defined by murine monoclonal antibodies. Cancer Res. 1985;45:826. [PubMed] [Google Scholar]
  • 25.Orlandi R, Canevari S, Leoni F, Mezzanzanica D, Ripamonti M, Colnaghi MI. Change in binding reactivity of an anti-tumor monoclonal antibody after the introduction of 2-pyridyl disulphide groups. Hybridoma. 1986;5:1. doi: 10.1089/hyb.1986.5.1. [DOI] [PubMed] [Google Scholar]
  • 26.Taetle R, Howell SB, Giuliani FC, Koziol J, Koessler A. Comparison of the activity of doxorubicin analogues using colony forming assays and human xenografts. Cancer. 1982;50:1445. doi: 10.1002/1097-0142(19821015)50:8<1455::aid-cncr2820500803>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  • 27.Tagliabue E, Ménard S, Della Torre G, Barbanti P, Mariani-Costantini R, Porro G, Colnaghi MI. Generation of monoclonal antibodies reacting with human epithelial ovarian cancer. Cancer Res. 1985;45:379. [PubMed] [Google Scholar]
  • 28.Tsuji Y, Suzuki T, Nishiura H, Takemura T, Isojima S. Identification of two different surface epitopes of human ovarian epithelial carcinomas by monoclonal antibodies. Cancer Res. 1985;45:2358. [PubMed] [Google Scholar]
  • 29.Young RC, Knapp RC, Perez CA. Cancer of the ovary. In: De Vita VTJ, Hellman S, Rosenberg SA, editors. Cancer principles and practice of oncology. Philadelphia: Lippincott Co JB; 1982. p. 884. [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES