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Thomsen-Friedenreich oncofetal antigen in Schistosoma mansoni: localization and immunogenicity in experimental mouse infection

  • C. THORS (a1) (a2), B. JANSSON (a3), H. HELIN (a4) and E. LINDER (a1) (a2)

Abstract

Our preliminary observation, that sera from schistosomiasis patients react with carcinomas, raised the possibility of antigenic cross-reactivity. We here extend this observation to show that mice experimentally infected with Schistosoma mansoni react with human urothelial and transitional bladder carcinomas and also with a gastric carcinoma cell line, AGS. To identify cross-reacting epitopes, we looked for the expression of carcinoma markers in schistosome worms and eggs using monoclonal antibodies against tumour antigens MUC1, Tn and TF (also known as the oncofetal Thomsen-Friedenreich antigen or T antigen). Immunohistochemical staining showed that the TF-epitope is present in adult intravascular S. mansoni worms and eggs deposited in tissues of infected animals. The localization of TF-immuno-reactive material in schistosomes was seen at the parasite surface between male and female worms and around trapped eggs in the liver. This localization is consistent with the antigen being secreted. Mice experimentally infected with S. mansoni, developed circulating antibodies against the TF-epitope (identified as Gal(beta1-3) GalNAc-O-R) as seen in ELISA using TF-expressing asialoglycophorin (AGP) as antigen. The observed anti-TF response in S. mansoni-infected mice reflects the complexity of host-parasite interactions in this infection.

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Corresponding author

Microbiology and Tumorbiology Center (MTC), Karolonska Institutet, Box 280, S-171 77 Stockholm, Sweden. Tel: +46 8 457 2520. Fax: +46 8 31 05 25. E-mail: ewert.linder@smi.ki.se

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REFERENCES

Baldus, S. E., Hanisch, F. G., Schwonzen, M., Nakahara, Y., Iijima, H., Ogawa, T., Peter-Katalinic, J. and Uhlenbruck, G. ( 1992). Monoclonal antibody SP-21 defines a sialosyl-Tn antigen expressed on carcinomas and K562 erythroleukemia cells. Anticancer Research 12, 19351940.
Barchi, J. J. ( 2000). Emerging roles of carbohydrates and glycomimetics in anticancer drug design [Review]. Current Pharmaceutical Design 6, 485501.
Barranco, S. C., Townsend, C. M. J., Casartelli, C., Macik, B. G., Burger, N. L., Boerwinkle, W. and Gourley, W. K. ( 1983). Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Research 43, 17031709.
Campbell, B. J., Finnie, I. A., Hounsell, E. F. and Rhodes, J. M. ( 1995). Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. Journal of Clinical Investigation 95, 571576.
Cao, Y., Stosiek, P., Springer, G. F. and Karsten, U. ( 1996). Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study. Histochemistry and Cell Biology 106, 197207.
Cheever, A., Kuntz, R., Moore, J. and Huang, T. ( 1988). Pathology of Schistosoma haematobium infection in the capuchin monkey (Cebus apella). Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 107111.
Chitsulo, L., Engels, D., Montresor, A. and Savioli, L. ( 2000). The global status of schistosomiasis and its control. Acta Tropica 77, 4151.
Cummings, R. D. and Nyame, A. K. ( 1999). Schistosome glycoconjugates. Biochimica et Biophysica Acta 1455, 363374.
Dahlenborg, K., Hultman, L., Carlsson, R. and Jansson, B. ( 1997). Human monoclonal antibodies specific for the tumour associated Thomsen-Friedenreich antigen. International Journal of Cancer 70, 6371.
Eberl, M., Langermans, J. A., Vervenne, R. A., Nyame, A. K., Cummings, R. D., Thomas, A. W., Coulson, P. S. and Wilson, R. A. ( 2001). Antibodies to glycans dominate the host response to schistosome larvae and eggs: is their role protective or subversive? Journal of Infectious Diseases 183, 12381247.
Eble, J., Sauter, G., Epstein, J. and Sesterhenn, I. ( 2004) World Health Organization. Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press, Lyon.
Fadden, A. J., Holt, O. J. and Drickamer, K. ( 2003). Molecular characterization of the rat Kupffer cell glycoprotein receptor. Glycobiology 13, 529537.
Hanisch, F. G. and Baldus, S. E. ( 1997). The Thomsen-Friedenreich (TF) antigen: a critical review on the structural, biosynthetic and histochemical aspects of a pancarcinoma-associated antigen. Histology and Histopathology 12, 263281.
Harris, J. R. and Markl, J. ( 1999). Keyhole limpet hemocyanin (KLH): a biomedical review [Review]. Micron 30, 597623.
Haslam, S. M., Coles, G. C., Morris, H. R. and Dell, A. ( 2000). Structural characterization of the N-glycans of Dictyocaulus viviparus: discovery of the Lewis(x) structure in a nematode. Glycobiology 10, 223229.
Hicks, R. M., James, C. and Webbe, G. ( 1980). Effect of Schistosomiasis haematobium and N-butyl-N-(4-hydroxybutyl)nitrosamine on the development of urothelial neoplasia in baboon. British Journal of Cancer 42, 730755.
Huang, H. H., Tsai, P. L. and Khoo, K. H. ( 2001). Selective expression of different fucosylated epitopes on two distinct sets of Schistosoma mansoni cercarial O-glycans: identification of a novel core type and Lewis X structure. Glycobiology 11, 395406.
Jacobs, W., Deelder, A. and Van Marck, E. ( 1999). Schistosomal granuloma modulation. II. Specific immunogenic carbohydrates can modulate schistosome-egg-antigen-induced hepatic granuloma formation. Parasitology Research 85, 1418.
Jurincic-Winkler, C. D., von der Kammer, H., Beuth, J., Scheit, K. H. and Klippel, K. F. ( 1996). Antibody response to keyhole limpet hemocyanin (KLH) treatment in patients with superficial bladder carcinoma. Anticancer Research 16, 21052110.
Kantelhardt, S. R., Wuhrer, M., Dennis, R. D., Doenhoff, M. J., Bickle, Q. and Geyer, R. ( 2002). Fuc(alpha1−>3)GalNAc-: the major antigenic motif of Schistosoma mansoni glycolipids implicated in infection sera and keyhole-limpet haemocyanin cross-reactivity. The Biochemical Journal 366, 217223.
Langkilde, N. C., Wolf, H., Clausen, H. and Orntoft, T. F. ( 1992). Human urinary bladder carcinoma glycoconjugates expressing T-(Gal beta(1–3)GalNAc alpha 1-O-R) and T-like antigens: a comparative study using peanut agglutinin and poly- and monoclonal antibodies. Cancer Research 52, 50305036.
Linder, E., Thors, C. and Lundin, L. ( 1991). Isolation of an SBA lectin-reactive glycoprotein (gp50) and its identification in Schistosoma mansoni larval and adult worm secretions. Journal of Parasitology 77, 391401.
MacLean, G. D. and Longenecker, B. M. ( 1991). Clinical significance of the Thomsen-Friedenreich antigen. Seminars in Cancer Biology 2, 433439.
Mostafa, M. H., Sheweita, S. A. and O'Connor, P. J. ( 1999). Relationship between schistosomiasis and bladder cancer. Clinical Microbiology Reviews 12, 97111.
Nyame, A. K., Lewis, F. A., Doughty, B. L., Correa-Oliveira, R. and Cummings, R. D. ( 2003). Immunity to schistosomiasis: glycans are potential antigenic targets for immune intervention. Experimental Parasitology 104, 113.
Polman, K., Stelma, F. F., Le Cessie, S., De Vlas, S. J., Falcao Ferreira, S. T., Talla, I., Deelder, A. M. and Gryseels, B. ( 2002). Evaluation of the patterns of Schistosoma mansoni infection and re-infection in Senegal, from faecal egg counts and serum concentrations of circulating anodic antigen. Annals of Tropical Medicine and Parasitology 96, 679689.
Ragupathi, G. ( 1996). Carbohydrate antigens as targets for active specific immunotherapy. Cancer Immunology and Immunotherapy 43, 152157.
Samuel, J., Noujaim, A. A., MacLean, G. D., Suresh, M. R. and Longenecker, B. M. ( 1990). Analysis of human tumor associated Thomsen-Friedenreich antigen. Cancer Research 50, 48014808.
Sell, S. ( 1990). Cancer-associated carbohydrates identified by monoclonal antibodies. Human Pathology 21, 10031019.
Shigeoka, H., Karsten, U., Okuno, K. and Yasutomi, M. ( 1999). Inhibition of liver metastases from neuraminidase-treated colon 26 cells by an anti-Thomsen-Friedenreich-specific monoclonal antibody. Tumour Biology 20, 139146.
Sobin, L. H. and Wittekind, C.h. ( 2002). TNM Classification of Malignant Tumours, Wiley-Liss, New York.
Springer, G. F. ( 1997). Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. Journal of Molecular Medicine 75, 594602.
Thors, C. and Linder, E. ( 1998). Cross-reacting antibodies against keyhole limpet haemocyanin may interfere with the diagnostics of acute schistosomiasis. Parasite Immunology 20, 489496.
Thors, C. and Linder, E. ( 2003). Localization and identification of Schistosoma mansoni/KLH-crossreactive components in infected mice. Journal of Histochemistry and Cytochemistry 51, 13671374.
van Dam, G. J., Claas, F. H., Yazdanbakhsh, M., Kruize, Y. C., van Keulen, A. C., Ferreira, S. T., Rotmans, J. P. and Deelder, A. M. ( 1996). Schistosoma mansoni excretory circulating cathodic antigen shares Lewis-x epitopes with a human granulocyte surface antigen and evokes host antibodies mediating complement-dependent lysis of granulocytes. Blood 88, 42464251.
WORLD HEALTH ORGANIZATION ( 1994). Evaluation of carcinogenic risk to humans. Schistosomes, liver flukes and Helicobacter pylori. IARC Monograph 61, 45119.
Wuhrer, M., Dennis, R. D., Doenhoff, M. J., Lochnit, G. and Geyer, R. ( 2000). Schistosoma mansoni cercarial glycolipids are dominated by Lewis X and pseudo-Lewis Y structures. Glycobiology 10, 89101.
Yu, L. G., Jansson, B., Fernig, D. G., Milton, J. D., Smith, J. A., Gerasimenko, O. V., Jones, M. and Rhodes, J. M. ( 1997). Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine). International Journal of Cancer 73, 424431.
Zhang, S., Zhang, H. S., Reuter, V. E., Slovin, S. F., Scher, H. I. and Livingston, P. O. ( 1998). Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. Clinical Cancer Research 4, 295302.

Keywords

Thomsen-Friedenreich oncofetal antigen in Schistosoma mansoni: localization and immunogenicity in experimental mouse infection

  • C. THORS (a1) (a2), B. JANSSON (a3), H. HELIN (a4) and E. LINDER (a1) (a2)

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