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Ultrastructural localization and internalization of proteoglycan epitopes in a human non-Hodgkin (B) lymphoma

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Summary

In a human non-Hodgkin (B) lymphoma xenograft (HT-117) heparan sulphate (HS) proved to be the main cell surface glycosaminoglycan, in contrast to the chondroitin sulphate dominance in normal lymphoid cells. Using anti-proteoglycan (PG) antibodies and immunoelectronmicroscopy, two heparan sulphate proteoglycans (transferrin receptor (TfR) and fibroblast membrane type) and one chondroitin sulphate proteoglycan (articular cartilage type) molecule were co-localized as random clusters on the surface of these lymphoma cells. Double labelling revealed that during internalization, which occurred via endosomes avoiding the lysosomal system, the different proteoglycan (PG) antigens became separated. The TfR and fibroblast membrane type HSPG epitopes reappeared on plasmalemmal vesicles derived most probably from the multivesicular endosomes, representing a unique form of exocytosis. It is suggested that different cell membrane PGs are integrated into subunits of yet unknown function in these human non-Hodgkin (B) lymphoma cells.

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References

  1. Carney SL (1986) Proteoglycans. In: Chaplin MF, Kennedy JF (eds) Carbohydrate analysis — a practical approach. IRL Press, Oxford, Washington, pp 97–140

  2. Cöster L, Carlstedt I, Kendall S, Malmström A, Schmidtchen A, Fransson L-Å (1986) Structure of proteoheparan sulfates from fibroblasts. J Biol Chem 261:12079–12088

  3. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I (1988) A heparin-binding angiogenic protein — basic fibroblast growth factor — is stored within basement membrane. Am J Pathol 130:393–399

  4. Giacoletto KS, Sant AJ, Bono C, Gorka J, O'Sullivan DM, Quaranta V, Schwartz BD (1986) The human invariant chain is the core protein of the human class II-associated proteoglycan. J Exp Med 164:1422–1439

  5. Glant TT, Mikecz K, Roughley PJ, Buzás E, Poole AR (1986) Age related changes in protein-related epitopes of human articular-cartilage proteoglycan. Biochem J 236:71–75

  6. Gordon J, Ley SC, Melamed MD, Åman P, Hughes-Jones NC (1984) Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus. J Exp Med 159:1554–1559

  7. Habeshaw JA, Lister TA, Stansfeld AG, Greaves MF (1983) Correlation of transferrin receptor expression with histological class and outcome in non-Hodgkin lymphoma. Lancet I:498–501

  8. Hart GW (1982) Biosynthesis of glycosaminoglycans by thymic lymphocytes. Effects of mitogenic activation. Biochemistry 24:6088–6097

  9. Iozzo RV (1988) Cell surface heparan sulfate proteoglycan and the neoplastic phenotype. J Cell Biochem 37:61–78

  10. Keating A, Gordon MY (1988) Hierarchical organization of hematopoetic microenvironments: role of proteoglycans. Leukemia 2:766–769

  11. Kopper L, Steel GG (1975) The therapeutic response of three human tumor lines maintained in immunosuppressed mice. Cancer Res 35:2704–2713

  12. Kopper L, Nagy P, Magyarosy E, Major J (1986) Chemotherapy of non-Hodgkin lymphoma (NHL) xenografts. Acta Morphol Hung 34:289–297

  13. Kopper L, Bánkfalvi A, Mihalik R, Pálóczy K, Benczúr M, Lapis K (1988) Phenotypic characteristics of three human non-Hodgkin lymphoma lines: flow cytometric analysis after longterm maintenance. Clin Exp Immunol 74:295–299

  14. Kopper L, Bánkfalvi A, Mihalik R, Glant T, Földi J, Nagy P (1989) Human non-Hodgkin lymphoma xenografts — a search for new markers. Pathol Res Pract 185:83

  15. Levitt D, Ho P-L (1983) Induction of chondroitin sulfate proteoglycan synthesis and secretion in lymphocytes and monocytes. J Cell Biol 97:351–358

  16. London L, Perussia B, Trinchieri G (1985) Induction of proliferation in vitro of resting human natural killer cells: expression of surface activation antigens. J Immunol 134:718–727

  17. Maciag T, Mehlman T, Friesel R, Schreiber AB (1984) Heparin binds endothelial growth factor, the principal endothelial cell mitogen in bovine brain. Science 225:932–935

  18. Neckers LM, Cossman J (1983) Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci USA 80:3494–3498

  19. Phillips JH, Le AM, Lauier LL (1984) Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens. J Exp Med 159:993–1008

  20. Pirker R, FitzGerald DJP, Hamilton TC, Ozols RF, Willingham MC, Pastan I (1985) Anti-transferrin receptor antibody linked to Pseudomonas exotoxin as a model immunotoxin in human ovarian carcinoma cell lines. Cancer Res 45:751–757

  21. Roberts R, Gallagher J, Spooncer E, Allen TD, Bloomfield F, Dexter TM (1988) Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature 332:376–378

  22. Saunders S, Bernfield M (1988) Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as receptor for interstitial matrix. J Cell Biol 106:423–430

  23. Schmidt RE, MacDermott RP, Bartley G, Bertovich M, Amato DA, Austen KF, Schlossman SF, Stevens RL, Ritz J (1985) Specific release of proteoglcyans from human natural killer cells during target lysis. Nature 318:289–291

  24. Seno S, Ono T, Tsujii T (1983) Macromolecular charge and cellular surface charge in adhesion, ingestion and blood vessel leakage. Ann NY Acad Sci 416:410–425

  25. Shau HY, Shen D, Golub SH (1986) The role of transferrin in natural killer cell and IL-2-induced cytotoxic cell function. Cell Immunol 97:121–130

  26. Sorrell JM, Lintala AM, Mahmoodian F, Caterson B (1988) Epitope-specific changes in chondroitin sulfate/dermatan sulfate proteoglycans as markers in the lymphopoietic and granulopoietic compartments of developing bursae of Fabricius. J Immunol 140:4263–4270

  27. Steck PA, Cheong PH, Nakajima M, Yung WKA, Moser RP, Nicolson GL (1987) Altered expression of glycosaminoglycans in metastatic 13762NF rat mammary adenocarcinoma cells. Biochemistry 26:1020–1028

  28. Timár J, McIntosh DP, Davies AJS, Lapis K (1987) Different approaches to target glycoconjugates in cancer therapy. In: Lapis K, Eckhardt S (eds) Molecular biology and differentiation of cancer cells. 14th International Cancer Congress, vol. 2. Académiai Kiadó, Budapest, pp 105–112

  29. Timár J, Móczár E, Timár F, Pál K, Kopper L, Lapis K, Jeney A (1987) Comparative study on Lewis lung tumor lines with “lwo” and “high” metastatic capacity. II. Cytochemical and biochemical evidence for differences in glycosaminoglycans. Clin Expl Metastasis 5:79–87

  30. Trowbridge IS, Domingo DL (1981) Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumour cells. Nature 294:171–173

  31. Turley EA, Tretiak M (1985) Glycosaminoglycan production by murine melanoma variants in vivo and in vitro. Cancer Res 45:5098–5105

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Correspondence to J. Timár.

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Timár, J., Kovalszky, I., Bánkfalvi, Á. et al. Ultrastructural localization and internalization of proteoglycan epitopes in a human non-Hodgkin (B) lymphoma. Histochemistry 94, 419–425 (1990). https://doi.org/10.1007/BF00266450

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Keywords

  • Lymphoma
  • Articular Cartilage
  • Transferrin
  • Lymphoma Cell
  • Heparan Sulphate