Skip to main content
SpringerLink
Log in

Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis

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

Abstract

PURPOSE: Recognition of metastatic tumor cells with distinct biochemical phenotypes predominant in the primary tumors should be useful not only for establishment of new therapeutic approaches but also for identification of highrisk or low-risk patients for relapse. We examined whether carbohydrate antigens, sialyl Lewisx (sLex) and sialyl Lewisa (sLea) are involved in colorectal cancer metastasis. METHODS: Metastatic abilities of human colon cancer cell variants that were selected for their high or low cell surface levels of sLex (KM12-HX and KM12-LX, respectively) were analyzed. Also, immunohistochemical expressions of sLex and sLea in 159 primary colorectal cancers were examined to determine the clinical significance of increased expression of these antigens. RESULTS: KM12-HX cells adhered more readily to tumor necrosis factor-α activated endothelial cells than did KM12-LX cells. Increased adhesion of KM12-HX cells to activated endothelial cells was inhibited by antibodies against E-selectin and sLex and by modification of cell surface carbohydrates. KM12-HX cells showed more invasive ability in vitro and more metastatic potential in the liver of nude mice than KM12-LX cells. Although no difference was seen in the expression of six messenger ribonucleic acids corresponding to progression or metastasis of colorectal cancer, expression of fucosyltransferase was found to be responsible for the higher expression of sLex in KM12-HX cells. Clinical records of patients showed that disease-free survival rate of patients with sLex-positive tumors was significantly poorer than that of those with sLex-negative tumors. Cox's multivariate analysis revealed that the sLex status was an independent predictive factor for disease recurrence (P = 0.004), depth of invasion (P = 0.0005), and histologic type> (P = 0.037), but sLea status, age, gender, tumor location, N stage, and vessel invasion were not. CONCLUSION: Increased expression of sLex could be involved in establishment of colorectal cancer metastasis. It appears that examining sLex expression may serve as a potent marker of the recurrence in patients with colorectal cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Eisenberg B, DeCosse JJ, Harford F, Michalek J. Carcinoma of the colon and rectum: the natural history reviewed in 1704 patients. Cancer 1982;49:1131–4.

    PubMed  Google Scholar 

  2. Galandiuk S, Wieand HS, Moertel CG,et al. Patterns of recurrence after curative resection of carcinoma of the colon and rectum. Surg Gynecol Obstet 1992;174:27–32.

    PubMed  Google Scholar 

  3. Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer—results of a prospectively randomized trial. N Engl J Med 1984;310:737–43.

    Google Scholar 

  4. National Institutes of Health Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1447–50.

    Google Scholar 

  5. Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science 1977;197:893–5.

    PubMed  Google Scholar 

  6. O'Connel MJ, Schaid DJ, Ganju V, Cunningham J, Kovach JS, Thibodeau ST. Current status of adjuvant chemotherapy for colorectal cancer. Cancer 1992;70:1732–9.

    PubMed  Google Scholar 

  7. Nicolson GL. Cancer metastasis: organ colonization and cell-surface properties of malignant cells. Biochem Biophys Acta 1982;695:113–76.

    PubMed  Google Scholar 

  8. Irimura T, Reading CL. Surface properties of metastatic tumor cells. Cancer Bull 1987;39:132–41.

    Google Scholar 

  9. Hakomori S. Aberrant glycosylation in tumors and tumor-associate carbohydrate antigens. Adv Cancer Res 1989;52:257–331.

    PubMed  Google Scholar 

  10. Fogel M, Altevogt P, Schirrmacher V. Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation. J Exp Med 1983;157:371–6.

    Article  PubMed  Google Scholar 

  11. Nabi IR, Watanabe H, Raz A. Identification of B16-F1 melanoma autocrine motility-like factor receptor. Cancer Res 1990;50:409–14.

    PubMed  Google Scholar 

  12. Miyake M, Hakomori S. A specific cell surface glycoconjugate controlling cell motility: evidence by functional monoclonal antibodies that inhibit cell motility and tumor cell metastasis. Biochemistry 1991;30:3328–34.

    Article  PubMed  Google Scholar 

  13. Dennis JW, Laferte S. Recognition of asparagine-linked oligosaccharides on murine tumor cells by natural killer cells. Cancer Res 1985;45:6034–40.

    PubMed  Google Scholar 

  14. Sherblom AP, Moody CE. Cell surface sialomucin and resistance to natural cell-mediated cytotoxicity of rat mammary tumor ascites cell. Cancer Res 1986;46:4543–6.

    PubMed  Google Scholar 

  15. Bolscher JM, Schallier DC, von Rooy H, Storme GA, Smets LA. Modification of cell surface carbohydrates and invasive behavior by a alkyl lysophospholipid. Cancer Res 1988;48:977–82.

    PubMed  Google Scholar 

  16. Irimura T, Ota DM, Cleary DR. Ulex europeus aggulitinin I-reactive high molecular weight glycoproteins of adenocarcinoma of distal colon and rectum and their possible relationship with metastatic potential. Cancer Res 1987;47:881–9.

    PubMed  Google Scholar 

  17. Itzkowitz SH, Yuan M, Fukushi Y,et al. Lewisx and sialylated Lewisx-related antigen expression in human malignant and non-malignant colonic tissues. Cancer Res 1986;46:2627–32.

    PubMed  Google Scholar 

  18. Hoff SD, Matsushita Y, Ota DM,et al. Increased expression of sialyl-dimeric Lex antigen in liver metastasis of human colorectal carcinoma. Cancer Res 1989;49:6883–8.

    PubMed  Google Scholar 

  19. Matsushita Y, Cleary KR, Ota DM, Hoff SD, Irimura T. Siaryl-dimeric Lewis-X antigen expression on mucinlike glycoproteins in colorectal cancer metastasis. Lab Invest 1990;63:780–91.

    PubMed  Google Scholar 

  20. Lowe JB, Stoollman LM, Nair RP, Larsen RD, Berhend TL, Marks RM. ELAM-1-dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell 1990;63:475–84.

    Article  PubMed  Google Scholar 

  21. Phillips ML, Nudelman E, Gaeta FC,et al. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science 1990;250:1130–2.

    PubMed  Google Scholar 

  22. Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B. Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Science 1990;250:1132–5.

    PubMed  Google Scholar 

  23. Takada A, Ohmori K, Takahashi N,et al. Adhesion of human cancer cells to vascular endothelium mediated by carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun 1991;179:713–9.

    Article  PubMed  Google Scholar 

  24. Fukushima K, Hirota M, Terasaki PI,et al. Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res 1984;44:5279–85.

    PubMed  Google Scholar 

  25. Sakamoto J, Watanabe T, Tokumaru,et al. Expression of Lewisa, Lewisb, Lewisx, Lewisy, sialyl-Lewisa, and sialyl-Lewisx blood group antigens in human gastric carcinoma and in normal gastric tissue. Cancer Res 1989;49:745–52.

    PubMed  Google Scholar 

  26. Miyake M, Zenita K, Tanaka O, Okada Y, Kannagi R. Stage-specific expression of SSEA-1-related antigens in the developing lung of human embryos and its relation to the distribution of these antigens in lung cancer. Cancer Res 1988;48:7150–8.

    PubMed  Google Scholar 

  27. Springer TA, Lasky LA. Sticky sugars for selections. Nature 1991;349:196–7.

    Article  PubMed  Google Scholar 

  28. Rice GD, Bevilacqua MP. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 1989;246:1303–6.

    PubMed  Google Scholar 

  29. Matsushita Y, Nakamori S, Seftor EA, Hendrix MJ, Irimura T. Human colon carcinoma cells with increased invasive capacity obtained by selection for sialyldimeric Lex antigen. Exp Cell Res 1991;196:20–5.

    Article  PubMed  Google Scholar 

  30. Morikawa K, Walker SM, Jessup JM, Fidler IJ.In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. Cancer Res 1988;48:1943–8.

    PubMed  Google Scholar 

  31. Salmon SE, Hamburger AW, Soehnlen B, Durie BG, Alberts DS, Moon TE. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med 1978;198:1321–7.

    Google Scholar 

  32. Hendrix MJ, Seftor EA, Seftor RE, Fidler IJ. A simple quantitative assay for studying the invasive potential of high and low human metastatic variants. Cancer Lett 1987;38:137–47.

    Article  PubMed  Google Scholar 

  33. Tokunaga K, Nakamura Y, Sakata K,et al. Enhanced expression of a glycelardehyde-3-phosphate dehydrogenase gene in human lung cancer. Cancer Res 1987;47:5616–9.

    PubMed  Google Scholar 

  34. Mafune K, Ravikumar TS, Wong JM, Yow H, Chen LB, Steel GD. Expression of Mr 32,000 laminin-binding protein messenger RNA in human colon carcinoma correlates with disease progression. Cancer Res 1990;50:3888–91.

    PubMed  Google Scholar 

  35. Elvin P, Kerr IB, McArdle CS, Birnie GD. Isolation and preliminary characterization of cDNA clones representing mRNA's associated with tumor progression and metastasis in colorectal cancer. Br J Cancer 1988;57:36–42.

    PubMed  Google Scholar 

  36. Levy AT, Cioce V, Sobel ME,et al. Increased expression of the Mr 72,000 Type IV collagenase in human colon adenocarcinoma. Cancer Res 1991;51:439–44.

    PubMed  Google Scholar 

  37. Verde P, Stoppelli MP, Galeffi P, Nocera PD, Blasi F. Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA. Proc Natl Acad Sci U S A 1984;8:4727–31.

    Google Scholar 

  38. Rosengard AM, Krutzsch HC, Shearn A,et al. Reduced Nm23/Awd protein in tumor metastasis and aberrant Drosophila development. Nature 1989;342:177–80.

    Article  PubMed  Google Scholar 

  39. Matlashewski G, Tuck S, Pim D, Schneider J, Crawford LV. Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol 1987;7:961–3.

    PubMed  Google Scholar 

  40. Kukowska-Latallo JF, Larsen RD, Nair RP, Lowe JB. A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and Lewis blood group α(1,3/1,4)fucosyltransferase. Genes Dev 1990;4:1288–303.

    PubMed  Google Scholar 

  41. Gendler S, Taylor-Papadimitriou J, Duhing T, Rothbard J, Burchell J. A highly immunogenic region of human polymorphic epithelial mucin expressed by carcinoma is made up of tandem repeats. J Biol Chem 1990;265:15286–93.

    PubMed  Google Scholar 

  42. Gum JR, Byrd JC, Hicks JW, Toribara NW, Lamport DT, Kim YS. Molecular cloning of human intestinal mucin cDNA. J Biol Chem 1989;264:6480–7.

    PubMed  Google Scholar 

  43. Harmanek P, Sobin LH, eds. TNM classification of malignant tumors: colon and rectum. 4th ed. Berlin: Springer-Verlag, 1987:47–9.

    Google Scholar 

  44. Fukushi Y, Nudelman E, Levery SB, Hakomori S, Rauvala H. Novel fucolipids accumulating in human adenocarcinoma. III. A hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside (VI3NeuAcV3III3Fuc2nLc6). J Biol Chem 1984;259:10511–7.

    PubMed  Google Scholar 

  45. Magnani JL, Nilsson B, Brockhaus M,et al. A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem 1982;257:1463–9.

    Google Scholar 

  46. Miyake M, Taki T, Hitomi S, Hakomori S. Correlation of expression of H/Lex/Leb antigen with survival in patients with carcinoma of the lung. N Engl J Med 1992;327:14–8.

    PubMed  Google Scholar 

  47. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457–81.

    Google Scholar 

  48. Mantel N. Evaluation of survival data and two new rank order statistics arising its consideration. Cancer Chemother Rep 1966;50:163–70.

    PubMed  Google Scholar 

  49. Cox DR. Regression models and life table. J Royal Stat Soc [B] 1972:34;187–220.

    Google Scholar 

  50. Holmes EH, Ostrander GK, Hakomori S. Biosynthesis of the sialyl-Lex determinant carried by Type 2 chain glycosphingolipids (IV3NeuAcIII,3FucnLc4 VI3NeuAcV,3FucnLc6 and VI3NeuAcIII3V3Fuc2nLc6) in human lung carcinoma PC9 cells. J Biol Chem 1986;261:3737–43.

    PubMed  Google Scholar 

  51. Hanski C, Drechsler K, Hanisc FG,et al. Altered glycosylation of MUC-1 protein core contributes to the colon carcinoma-associated increase of mucin-bound sialylLewisx expression. Cancer Res 1993;53:4082–8.

    PubMed  Google Scholar 

  52. Hanski C, Hanski ML, Zimmer T, Ogorek D, Devine P, Riecken EO. Characterization of major sialyl-Lex-positive mucins present in colon, colon carcinoma, and sera of patients with colorectal cancer. Cancer Res 1995;55:928–33.

    PubMed  Google Scholar 

  53. Hakomori S. Aberrant glycosylation in tumors and tumor associated-carbohydrate antigens. Adv Cancer Res 1989;52:257–331.

    PubMed  Google Scholar 

  54. Chia D, Terasaki PI, Suyama N, Galton J, Hirota M, Kartz D. Use of monoclonal antibodies to sialylated Lewisx and sialylated Lewisa for serological tests of cancer. Cancer Res 1985;45:435–53.

    PubMed  Google Scholar 

  55. Kannagi R, Fukushi Y, Tachikawa T,et al. Quantitative and qualitative characterization of human cancerassociated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl Type 2 chain polylactosamine. Cancer Res 1986;46:2619–26.

    PubMed  Google Scholar 

  56. Hakomori S. Possible functions of tumor-associated carbohydrate antigens. Curr Opin Immunol 1991;3:646–53.

    Article  PubMed  Google Scholar 

  57. Fidler IJ, Radinsky R. Genetic control of cancer metastasis [Editorial]. J Natl Cancer Inst 1990;82:166–8.

    PubMed  Google Scholar 

  58. Hart IR, Goode NT, Wilson RE. Molecular aspects of the metastatic cascade. Biochem Biophys Acta 1989;989:65–84.

    PubMed  Google Scholar 

  59. Hill RP. Genetic aspects of metastasis. Curr Opin Oncol 1990;2:157–62.

    PubMed  Google Scholar 

  60. Berg EL, Robinson MK, Mansson O, Butcher EC, Magnani JL. A carbohydrate domain common to both sialyl Lea and sialyl Lex is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1. J Biol Chem 1991;266:14869–72.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-1-1 Nakamichi, Higashinari-Ku, 537, Osaka, Japan

    Shoji Nakamori M.D., Masao Kameyama M.D., Shingi Imaoka M.D., Hiroshi Furukawa M.D., Osamu Ishikawa M.D. & Yo Sasaki M.D.

  2. Department of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan

    Yuki Izumi M.S. & Tatsuro Irimura Ph.D.

Authors
  1. Shoji Nakamori M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masao Kameyama M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shingi Imaoka M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroshi Furukawa M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Osamu Ishikawa M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yo Sasaki M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuki Izumi M.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tatsuro Irimura Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, Japan. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.

About this article

Cite this article

Nakamori, S., Kameyama, M., Imaoka, S. et al. Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis. Dis Colon Rectum 40, 420–431 (1997). https://doi.org/10.1007/BF02258386

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02258386

Key words

Search

Navigation