Clinical & Experimental Metastasis

, Volume 12, Issue 4, pp 324–328 | Cite as

Metastatic potential of human colorectal carcinoma SW1222 cells transfected with cDNA encoding carcinoembryonic antigen

  • Junko Hashino
  • Yoshiaki Fukuda
  • Shinzo Oikawa
  • Hiroshi Nakazato
  • Toshihiro Nakanishi
Article

Abstract

In order to examine a role of carcinoembryonic antigen (CEA) in metastasis, cDNA encoding CEA was introduced into a clone of human colorectal carcinoma SW1222 cells. Western blot analysis revealed that all transfectants express CEA of 180 kDa while the parent clone does not. In the transfectants, the level of CEA expression in clone 3 was higher than that of clone 1. Clone 3 formed aggregates rapidly after suspended by trypsinization while clone 1 did not. In experimental metastasis assay where tumor cells were injected intrasplenically, clone 3 exhibited a higher liver-metastatic activity than clone 1. Fab fragment of anti-CEA antibody significantly inhibited both the cell aggregation and the liver metastases caused by clone 3. These findings suggested that CEA expressed on the cell surface may play an important role in hepatic metastasis from colorectal carcinoma, possibly through its cell adhesion activity.

Keywords

carcinoembryonic antigen cell adhesion liver metastasis 

References

  1. 1.
    Gold P and Freedman SO, 1965, Demonstration of tumor-specific antigens in human colonic carcinoma by immunological tolerance and absorption techniques.J Exp Med,121, 439–62.PubMedGoogle Scholar
  2. 2.
    Oikawa S, Nakazato H and Kosaki G, 1987, Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence.Biochem Biophys Res Commun,142, 511–8.PubMedGoogle Scholar
  3. 3.
    Zimmerman W, Ortlieb B, Friedrich R and Von Kleist S, 1987, Isolation and characterization of cDNA clones encoding the human carcinoembryonic antigen reveal a highly conserved repeating structure.Proc Natl Acad Sci USA,84, 2960–64.PubMedGoogle Scholar
  4. 4.
    Beauchemin N, Benchimol S, Cournoyer D, Fuks A and Stanners CP, 1987, Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen.Mol Cell Biol,7, 3221–30.PubMedGoogle Scholar
  5. 5.
    Oikawa S, Imajo S, Noguchi T, Kosaki G and Nakazato H, 1987, The carcinoembryonic antigen (CEA) contains multiple immunoglobulin-like domains.Biochem Biophys Res Commun,144, 634–42.PubMedGoogle Scholar
  6. 6.
    Paxton RJ, Mooser G, Pande H, Lee TD and Shively JE, 1987, Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family.Proc Natl Acad Sci USA,84, 920–24.PubMedGoogle Scholar
  7. 7.
    Benchimol S, Fuks A, Jothy S,et al. 1989, Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule.Cell,57, 327–34.PubMedGoogle Scholar
  8. 8.
    Oikawa S, Inuzuka C, Kuroki M,et al. 1989, Cell adhesion activity of non-specific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: homophilic and heterophilic adhesion.Biochem Biophys Res Commun,164, 39–45.PubMedGoogle Scholar
  9. 9.
    Humphries MJ, Olden K and Yamada KM, 1986, Synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells.Science,233, 467–70.PubMedGoogle Scholar
  10. 10.
    McCarthy JB, Skubitz APN, Palm SL and Furcht LT, 1988, Metastases inhibition of different tumor types by purified laminin fragments and a heparinbinding fragment of fibronectin.J Natl Cancer Inst,80, 108–16.PubMedGoogle Scholar
  11. 11.
    Roossien FF, De Kuiper PE, De Rijk D and Roos E, 1990, Invasive and metastatic capacity of revertants of LFA-1-deficient mutant T-cell hybridomas.Cancer Res,50, 3509–13.PubMedGoogle Scholar
  12. 12.
    Hostetter RB, Augustus LB, Mankarious R,et al. 1990, Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis.J Natl Cancer Inst,82, 380–85.PubMedGoogle Scholar
  13. 13.
    Southern PJ and Berg P, 1982, Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.J Mol Appl Genet,1, 327–41.PubMedGoogle Scholar
  14. 14.
    Kozlowski JM, Fidler IJ, Campbell D,et al. 1984, Metastatic behavior of human tumor cell lines grown in the nude mouse.Cancer Res,44, 3522–9.PubMedGoogle Scholar
  15. 15.
    Wagner HE, Toth CA, Steele G Jr and Thomas P, 1992, Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.Clin Exp Metastasis,10, 25–31.PubMedGoogle Scholar
  16. 16.
    Steele G Jr and Zamcheck N, 1985, The use of carcinoembryonic antigen in the clinical management of patients with colorectal cancer.Cancer Detect Prev,8, 421–7.PubMedGoogle Scholar
  17. 17.
    Thomas P, Toth CA, Saini KS, Jessup JM and Steele G Jr, 1990, The structure, metabolism and function of the carcinoembryonic antigen gene family.Biochim Biophys Acta,1032, 177–89.PubMedGoogle Scholar
  18. 18.
    Updike TV and Nicolson GL, 1986, Malignant melanoma cell lines selectedin vitro for increased homotypic adhesion properties have increased experimental metastatic potential.Clin Exp Metastasis,4, 273–84.PubMedGoogle Scholar
  19. 19.
    Shuster J, Silverman M and Gold P, 1973, Metabolism of human carcinoembryonic antigen in xenogeneic animals.Cancer Res,33, 65–8.PubMedGoogle Scholar
  20. 20.
    Thomas P and Hems DA, 1975, Hepatic clearance of circulating native and asialo carcinoembryonic antigen by the rat.Biochem Biophys Res Commun,67, 1205–9.PubMedGoogle Scholar
  21. 21.
    Toth CA, Thomas P, Broitman SA and Zamcheck N, 1982, A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat.Biochem J,204, 377–81.PubMedGoogle Scholar
  22. 22.
    Bresalier RS, Hujanen ES, Raper SE,et al. 1987, An animal model for colon cancer metastasis: establishment and characterization of murine cell lines with enhanced liver-metastasizing ability.Cancer Res,47, 1398–406.PubMedGoogle Scholar

Copyright information

© Rapid Communications of Oxford Ltd 1994

Authors and Affiliations

  • Junko Hashino
    • 1
  • Yoshiaki Fukuda
    • 1
  • Shinzo Oikawa
    • 1
  • Hiroshi Nakazato
    • 1
  • Toshihiro Nakanishi
    • 1
  1. 1.Suntory Institute for Biomedical ResearchOsakaJapan

Personalised recommendations