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Cancer Therapy pp 259-267 | Cite as

The Mechanism of Lectin-Mediated Adhesion of Human Ovarian Carcinoma Cells

  • R. J. Bernacki
Conference paper
Part of the NATO ASI Series book series (volume 75)

Abstract

Tumor invasion, dissemination and the subsequent formatlon of metastatic foci derive from alteratlons in tumor cell adheslveness. Lectins and other intercellular adhesion molecules (ICAMs) are involved in establishlng adhesion between tumor cells, vascular endothelial cells and the basement membrane. Galaptin, an endogenous lectin with affinity for galactose containing oligosaccharides, is present in the extracellular matrlx (ECM) and participates in the binding of A121 human ovarian carcinoma cells to the ECM. The specificity for galactose was demonstrated by inhibiting binding with lactose and by pretreating A121 cells with β-galactosidase. We have now carried out studies to identlfy the cellular glycoprotein(s) that are responslble for binding A121 cells to galaptin. Our results indicate that the galaptin receptor on the ovarian tumor cell surface is a hlghly glycosylated, lysosome-associated membrane protein (lamp). A series of membrane sugar analogs has been deslgned and synthesized as potential modulators of the galaptin receptor. One analog, 2-acetamldo-1, 4, 6-tri-0-acetyl-3-deoxy-3-fluoro-glucosamine (CD 89029), was found to specifically inhibit glycoprotein biosynthesls. As a result of this inhibition, tumor cells treated with CD 89029 decreased their adhesion to the ECM. These studies show that tumor cell adhesion is medlated by specific endogenous lectins and their cell surface glycoconjugate receptors (i.e. lamp), and that appropriate sugar analogs can serve as potential Inhibitors of metastatic spread.

Keywords

A121 Cell Tumor Cell Adhesion Roswell Park Cancer Institute Human Ovarian Carcinoma Cell Endogenous Lectin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allen HG, Sucato D, Woynarowska B, Gottstine S, Sharma A, Bernacki RJ (1990) Role of galaptin in ovarian carcinoma adhesion to extracellular matrix, J Cell Biochem 43, 43–57PubMedCrossRefGoogle Scholar
  2. Butcher EC (1991) Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity, Cell 67, 1033–1036PubMedCrossRefGoogle Scholar
  3. Carlsson SR, Fukuda M (1990) The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2, J Biol Chem 265, 20488–20495PubMedGoogle Scholar
  4. Crickard K, Niedbala MJ, Crickard U, Yoonessi M, Sandberg AA, Okuyama K, Bernacki RJ, Satchidanand (1989) Characterization of human ovarian and endometrial carcinoma cell lines established on extracellular matrix, Gynecol Oncol 32, 163–173Google Scholar
  5. Gospodarowicz D, Mescher AL, Burdwell CR (1977) Stimulation of corneal endothelial cell proliferation in vitro by fibroblast and epidermal growth factors, Exp Eye Res 25, 75–89PubMedCrossRefGoogle Scholar
  6. Leto G, Tumminello FM, Gebbia N, Woynarowska B, Bernacki RJ (1990) Antimetastatic activity of adriamycin in combination with protease inhibitors in mice, Anticancer Res 10, 265–270PubMedGoogle Scholar
  7. Niedbala M, Crickard K, Bernacki R (1987) In vitro degradation of extracellular matrix by human ovarian tumor cells, Clin Expl Metastasis 5, 181–197CrossRefGoogle Scholar
  8. Niedbala MJ, Crickard K, Bernacki RJ (1985) Interactions of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix: An in vitro model system for studying tumor cell adhesion and invasion, Exp Cell Res 160, 499–513PubMedCrossRefGoogle Scholar
  9. Phillips ML, Nudelman E, Gaeta FCA, Perez M, Singhal AK, Hakomori S-I, Paulson JC (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-le, Science 250, 1130–1135PubMedCrossRefGoogle Scholar
  10. Polley MJ, Phillips ML, Wayner E, Nudelman E, Singhal AK, Hakomori S-I, Paulson JC (1991) CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x, Proc Natl Acad Sci 88, 6224–6228PubMedCrossRefGoogle Scholar
  11. Sharma M, Bernacki RJ, Korytnyk W (1988) Fluorinated analogs of cell-surface carbohydrates as potential chemotherapeutic agents. In: Taylor NF (ed) Fluorinated Carbohydrates: Chemical and Biochemical Aspects ACS Symposium Series No. 374 Chapter 11. American Chemical Society, Washington DC, pp 191–206CrossRefGoogle Scholar
  12. Skrincosky DM, Allen HJ, Bernacki RJ (1993) Galaptin mediated adhesion of human ovarian carcinoma A121 cells, Cancer Research (In Press)Google Scholar
  13. Springer TA (1990) Adhesion receptors of the Immune system, Nature 346, 425–434PubMedCrossRefGoogle Scholar
  14. Woynarowska B, Hlkiel H, Bernacki RJ (1989) Human ovarian carcinoma β-N-acetylglucosaminidase isoenzymes and their role in extracellular matrix degradation, Cancer Research 49, 5598–5604.PubMedGoogle Scholar
  15. Woynarowska B, Wikiel H, Sharma M, Carpenter N, Fleet GWJ, Bernacki RJ (1992) Inhibition of human ovarian carcinoma cell- and hexosaminidase-mediated degradation of extracellular matrix by sugar analogs. Anticancer Res 12, 161–166PubMedGoogle Scholar
  16. Youakim A, Romero PA, Yee K, Carlsson SR, Fukuda M, Herscovics A (1989) Decrease in polylactosaminoglycans associated with lysosomal membrane glycoproteins during differentiation of CaCo-2 human colonic adenocarcinoma cells, Cancer Research 49, 6889–6895PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • R. J. Bernacki
    • 1
    • 2
  1. 1.Department of Experimental TherapeuticsRoswell Park Cancer Institute BuffaloBuffaloUSA
  2. 2.Department of Experimental TherapeuticsRoswell Park Cancer InstituteBuffaloUSA

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