Skip to main content

Advertisement

Log in

Adhesive function of carcinoembryonic antigen in the liver metastasis of KM-12c colon carcinoma cell line

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: Both experimental and clinical results reveal that carcinoembryonic antigen (CEA) seems to mediate some important role in the liver metastasis of colorectal carcinoma cells. The intent of this study was to verify whether adhesive function of CEA might affect liver metastasis in the CEA-expressing colon carcinoma cell line, KM-12c. METHODS: The hepatic binding of [125I]iododeoxyuridine KM-12c cells was measured with or without intravenous CEA pretreatment in four nude mice each. Then, 2×106 cells of KM-12c were injected into the splenic subcapsule of 57 CEA-pretreated nude mice. KM-12c cells were prepared in phosphate-buffered saline (control, 27 mice) or anti-CEA monoclonal antibody, T84.66 (30 mice). All mice were killed at the end of the eighth week after implant, and tumor nodules were confirmed histologically. RESULTS: Marginal differences of hepatic sequestration were found between the CEA-pretreated mice and the control group. Splenic tumor occurred in 75 percent (18/24) of the control group and in 40 percent (10/25) of the T84.66-pretreated group (P=0.0107). Forty-two percent (10/24) incurred liver metastasis in the control group, whereas 20 percent (5/25) did so in the T84.66-pretreated group. The number of splenic tumor cells was significantly related to the number and volume of liver metastasis (P=0.0065). CONCLUSIONS: CEA enhanced liver metastasis predominantly by successful primary tumor implant, whereas primary hepatic entrapment also supported it to some extent in a weakly metastatic colon carcinoma cell line, KM-12c. Tumor cell aggregates seem to be mediated by homophilic binding of CEA molecules, and it is an important mechanism to yield liver metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Willis RA. Spread of tumors in the human body. Woburn: Butterworths, 1973.

    Google Scholar 

  2. Hart IR. Seed and soil revisited: mechanism of sitespecific metastasis. Cancer Metastasis Rev 1982;1:5–17.

    Article  PubMed  CAS  Google Scholar 

  3. Tarin D, Price JE, Kettlewell MG, Souter RG, Vass AC, Crossley B. Clinicopathological observations on metastasis in man studied in patients treated with peritoneovenous shunts. BMJ 1984;288:749–51.

    Article  PubMed  CAS  Google Scholar 

  4. Medoff JR, Clark VD, Roche JK. Characterization of an immunosuppressive factor from malignant ascites that resembles a factor inducedin vitro by CEA in patients. Cancer Res 1988;48:1689–92.

    PubMed  Google Scholar 

  5. Hakim A. CEA antigen, a tumor associated glycoprotein, induces defective lymphocyte function. Neoplasma 1984;31:385–97.

    PubMed  CAS  Google Scholar 

  6. Heiskala MK, Stenman UH, Koivunen E, Carpen O, Saksela E, Timonen T. Characteristics of soluble tumorderived proteins that inhibit natural killer activity. Scand J Immunol 1988;28:19–27.

    PubMed  CAS  Google Scholar 

  7. Hostetter RB, Campbell DE, Chi K,et al. Carcinoembryonic antigen enhances metastatic potential of human colorectal carcinoma. Arch Surg 1990;125:300–4.

    PubMed  CAS  Google Scholar 

  8. Hostetter RB, Augustus LB, Mankarious R,et al. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Natl Cancer Inst 1990;82:380–5.

    PubMed  CAS  Google Scholar 

  9. Jessup JM, Kim JC, Thomas P,et al. Adhesion to carcinoembryonic antigen by human colorectal carcinoma cells involves at least two epitopes. Int J Cancer 1993;55:262–8.

    PubMed  CAS  Google Scholar 

  10. Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 1989;57:327–34.

    Article  PubMed  CAS  Google Scholar 

  11. Oikawa S, Inuzuka C, Kuroki M, Matsuoka Y, Kosaki G, Nakazato H. 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 1989;164:39–45.

    Article  PubMed  CAS  Google Scholar 

  12. Juliano RL. Membrane receptors for extracellular matrix macromolecules: relationship to cell adhesion and tumor metastasis. Biochim Biophys Acta 1987;907:261–78.

    PubMed  CAS  Google Scholar 

  13. McCarthy JB, Basara ML, Palm SI. The role of cell adhesion proteins laminin and fibronectin in the movement of malignant and metastatic cells. Cancer Metastasis Rev 1985;4:125–52.

    Article  PubMed  CAS  Google Scholar 

  14. Jessup JM, Giavazzi R, Campbell D, Cleary K, Morikawa K, Fidler IJ. Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. Cancer Res 1988;48:1689–92.

    PubMed  CAS  Google Scholar 

  15. Giavazzi R, Jessup MJ, Campbell DE, Walker SM, Fidler IJ. Experimental nude mouse model of human colorectal cancer liver metastases. J Natl Cancer Inst 1986;77:1303–8.

    PubMed  CAS  Google Scholar 

  16. Jessup JM, Petrick AP, Toth CA,et al. Carcinoembryonic antigen: enhancement of liver colonization through retension of human colorectal carcinoma cells. Br J Cancer 1993;67:464–70.

    PubMed  CAS  Google Scholar 

  17. Thomas P, Petrick AT, Toth CA, Fox ES, Elting JJ, Steele G Jr. A peptide sequence on carcinoembryonic antigen bind to a 80kD protein on Kupffer cells. Biochem Biophys Res Commun 1992;188:671–7.

    Article  PubMed  CAS  Google Scholar 

  18. Hass GN, Bolling TJ, Kinders RJ,et al. Preparation of synthetic polypeptide domains of carcinoembryonic antigen and their use in epitope mapping. Cancer Res 1991;51:1876–82.

    PubMed  CAS  Google Scholar 

  19. Giavazzi R, Campbell DE, Jessup JM, Cleary K, Fidler IJ. Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice. Cancer Res 1986;46:1928–33.

    PubMed  CAS  Google Scholar 

  20. Bym RA, Medrek P, Thomas P, Jeanloz R, Zamcheck N. Effect of heterogeneity of CEA on liver cell membrane binding and its kinetics of removal from circulation. Cancer Res 1985;45:3137–42.

    PubMed  Google Scholar 

  21. Hammarstrom S, Shively JE, Paxton RJ,et al. Antigenic sites in carcinoembryonic antigen. Cancer Res 1989;49:4852–8.

    PubMed  CAS  Google Scholar 

  22. Levin LV, Griffin TW. Specific adhesion of carcinoembryonoic antigen-bearing colorectal cancer cells to immobilized carcinoembryonic antigen. Cancer Lett 1991;60:143–52.

    Article  PubMed  CAS  Google Scholar 

  23. Ljubimov AV, Krutovskikh VA. Distribution of laminin and collagen type IV in rat colon tumors induced by 1,2-dimethylhydrazine. Invasion Metastasis 1987;7:61–72.

    PubMed  CAS  Google Scholar 

  24. Bouziges F, Simo P, Simon-Assmann P, Haffen K, Kedinger M. Altered deposition of basement-membrane molecules in co-culture of colonic cancer cells and fibroblasts. Int J Cancer 1991;48:101–8.

    Article  PubMed  CAS  Google Scholar 

  25. Jimenz RA, Mannik M. Evaluation of aggregated IgG in mice as an Fc receptor specific probe of the hepatic mononuclear phagocyte system. Clin Exp Immunol 1982;49:200–8.

    PubMed  Google Scholar 

  26. Behr T, Becker W, Hannappel E, Goldenberg DM, Wolf F. Targeting of liver metastases of colorectal cancer with IgG, F(ab2, and Fabanti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics. Cancer Res 1995;55:5777–85.

    Google Scholar 

  27. Pignatelli M, Durbin H, Bodmer WF. Carcinoembryonic antigen functions as an accessory adhesion molecule mediating colon epithelial cell collagen interaction. Proc Natl Acad Sci U S A 1990;87:1541–5.

    PubMed  CAS  Google Scholar 

  28. Terranova VP, Hujanen ES, Martin R. Basement membrane and the invasive activity of metastatic tumor cells. J Natl Cancer Inst 77;1986:311–6.

    PubMed  CAS  Google Scholar 

  29. Hefta LJ, Chen FS, Ronk M,et al. Expression of carcinoembryonic antigen and its predicted immunoglobulin-like domains in HeLa cells for epitope analysis. Cancer Res 52;1992:5647–55.

    PubMed  CAS  Google Scholar 

  30. Zhou H, Fuks A, Alcaraz G, Bolling TJ, Stanners CP. Homophilic aggregation between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds. J Cell Biol 1993;122:951–60.

    Article  PubMed  CAS  Google Scholar 

  31. Ohannesian DW, Lotan D, Thomas P,et al. Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells. Cancer Res 1995;1995:2191–9.

    Google Scholar 

  32. Fudler IJ. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with125I-5-iodo-2deoxyuridine. J Natl Cancer Inst 1970;45:773–82.

    PubMed  Google Scholar 

  33. Updyke TV, Nicolson GL. Malignant melanoma cell lines selectedin vitro for increased homotypic adhesion properties have increased experimental metastatic potential. Clin Exp Metastasis 1986;4:273–84.

    Article  PubMed  CAS  Google Scholar 

  34. Thomas P, Petrick AT, Toth CA, Fox ES, Elting JJ, Steele G Jr. A peptide on carcinoembryonic antigen binding to a 80kD protein on Kupffer cells. Biochem Biophys Res Commun 1992;188:671–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Asan Foundation Grant, 1996–1997, Asan Institute for Life Sciences, Seoul, Korea.

About this article

Cite this article

Kim, J.C., Roh, S.A. & Park, K.C. Adhesive function of carcinoembryonic antigen in the liver metastasis of KM-12c colon carcinoma cell line. Dis Colon Rectum 40, 946–953 (1997). https://doi.org/10.1007/BF02051203

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02051203

Key words

Navigation