Breast Cancer Research and Treatment

, Volume 101, Issue 2, pp 161–174 | Cite as

Lewis x Antigen Mediates Adhesion of Human Breast Carcinoma Cells to Activated Endothelium. Possible Involvement of the Endothelial Scavenger Receptor C-type Lectin

  • María Teresa Elola
  • Mariana Isabel Capurro
  • María Marcela Barrio
  • Peter J. Coombs
  • Maureen E. Taylor
  • Kurt Drickamer
  • José Mordoh
Preclinical Study

Abstract

Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.

Keywords

Lewis x (CD15), Monoclonal antibodies FC 2.15 and MCS 1, MCF 7, PMN, Scavenger receptor C type lectin 

Abbreviations

Ags

antigens

C′

complement

CD

Cluster of Differentiation

CDC

complement-dependent cytotoxicity

CEA

carcinoembryonic antigen

CEA-CAM-1

carcinoembryonic antigen-related cell adhesion molecule 1

DC

dendritic cell

DC-SIGN

dendritic cell-specific [intercellular adhesion molecule]-3- grabbing nonintegrin

2dGlc

2-deoxy-d-glucose

FACS

Fluorescence-activated cell sorting

FITC

fluorescein isothiocyanate

fMLP

N-formyl-methionyl-leucyl-phenylalanine

HUVEC

human umbillical vein endothelial cells

IAA

iodoacetic acid

ICAM-3

intercellular adhesion molecule-3

LPS

lipopolysaccharide

Lex

Lewis x

Galβ1–4(Fucα1–3) GlcNAc

Lewis x

Lea

Lewis a

Galβ1–3(Fucα1–4) GlcNAc

Lewis a

sLex

Silayl-Lewis x

NeuAcα2–3 Galβ1– 4(Fucα1–3) GlcNAc

Silayl-Lewis x

mAb

monoclonal antibody

PBS

phosphate buffered saline

PMN

polymorphonuclear neutrophils

PMSF

phenyl-methyl-sulfonyl-fluoride

SRCL

scavenger receptor C-type lectin

SSEA-1

stage specific embryonic antigen 1

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References

  1. 1.
    Gooi HC, Feizi T, Kapadia A, Knowles BB, Solter D, Evans MJ (1981) Stage-specific embryonic antigen involves α1→3 fucosylated type 2 blood group chains. Nature 292:156–158PubMedCrossRefGoogle Scholar
  2. 2.
    Hakomori S, Nudelman E, Levery S, Solter D, Knowles BB (1981) The hapten structure of a developmentally regulated glycolipid antigen (SSEA-1) isolated from human erytrocytes and adenocarcinoma: a preliminary note. Biochem Biophys Res Commun 100:1578–1586PubMedCrossRefGoogle Scholar
  3. 3.
    Spooncer E, Fukuda M, Klock JC, Oates JE, Dell A (1984) Isolation and characterization of polyfucosylated lactosaminoglycan from human granulocytes. J Biol Chem 259:4792–4801PubMedGoogle Scholar
  4. 4.
    Mordoh J, Leis S, Bravo AI, Podhajcer OL, Ballaré C, Capurro M, Kairiyama C, Bover L (1994) Description of a new monoclonal antibody, FC-2.15, reactive with human breast cancer and other human neoplasia. Int J Biological Markers 9:125–134Google Scholar
  5. 5.
    Hittelet A, Camby I, Nagy N, Legendre H, Bronckart Y, Decaestecker C, Kaltner H, Nifant’ev NE, Bovin NV, Pector JC, Salmon I, Gabius HJ, Kiss R, Yeaton P (2003) Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration. Lab Invest 83:777–787PubMedGoogle Scholar
  6. 6.
    Ohana-Malka O, Benharroch D, Isakov N, Prinsloo I, Shubinsky G, Sacks M, Gopas J (2003) Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin’s lymphoma-derived cell lines. Exp Hematol 31:1057–1065PubMedCrossRefGoogle Scholar
  7. 7.
    Rizzatti EG, Portieres FL, Martins SL, Rego EM, Zago MA, Falcao RP (2004) Microgranular and t(11;17)/PLZF-RARalpha variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34 and CD15 expression characteristic of PML-RARalpha gene rearrangement. Am J Hematol 76:44–51PubMedCrossRefGoogle Scholar
  8. 8.
    Johnston DS, Wright WW, Shaper JH, Hokke CH, Van den Eijnden DH, Joziasse DH (1998) Murine sperm-zona binding, a fucosyl residue is required for a high affinity sperm-binding ligand. A second site on sperm binds a nonfucosylated, beta-galactosyl-capped oligosaccharide. J Biol Chem 273:1888–1895PubMedCrossRefGoogle Scholar
  9. 9.
    D’Costa S, Petitte J-N (1999) Characterization of stage-specific embryonic antigen-1 (SSEA-1) expression during early development of the turkey embryo. Int J Dev Biol 43:349–356Google Scholar
  10. 10.
    Allendoerfer KL, Durairaj A, Matthews GA, Patterson PH (1999) Morphological domains of Lewis X-FORSE 1 immunolabeling in the embryonic neural tube are due to developmental regulation of cell surface carbohydrate expression. Dev Biol 211:208–219PubMedCrossRefGoogle Scholar
  11. 11.
    Geijtenbeek TB, Van Vliet SJ, Engering A, Ba TH, Van Kooyk Y (2004) Self- and non-self-recognition by C-type lectins on dendritic cells. Annu Rev Immunol 22:33–54PubMedCrossRefGoogle Scholar
  12. 12.
    van Gisbergen KP, Aarnoudse CA, Meijer GA, Geijtenbeek TB, van Kooyk Y (2005) Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin. Cancer Res 65:5935–5944PubMedCrossRefGoogle Scholar
  13. 13.
    Kannagi R, Isawa M, Koike T, Miyazaki K, Kimura N (2004) Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 95:377–384PubMedCrossRefGoogle Scholar
  14. 14.
    Vestweber D, Blanks JE (1999) Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213PubMedGoogle Scholar
  15. 15.
    Giavazzi R, Foppolo M, Dossi R, Remuzzi A (1993) Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions. J Clin Invest 92:3038–3044PubMedCrossRefGoogle Scholar
  16. 16.
    Kitayama J, Tsuno N, Sunami E, Osada T, Muto T, Nagawa H (2000) E-selectin can mediate the arrest type of adhesion of colon cancer cells under physiological shear flow. Eur J Cancer 36:121–127PubMedCrossRefGoogle Scholar
  17. 17.
    Burdick MM, McCaffery JM, Kim YS, Bochner BS, Konstantopoulos K (2003) Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow. Am J Physiol Cell Physiol 284:C977-C987PubMedGoogle Scholar
  18. 18.
    Mitoma J, Petryniak B, Hiraoka N, Yeh J-C, Lowe JB, Fukuda M (2003) Extended core 1 and core 2 branched O-glycans differentially modulate sialyl Lewis x-type L-selectin ligand activity. J Biol Chem 278:9953–9961PubMedCrossRefGoogle Scholar
  19. 19.
    Skubitz KM, Snook RW (1987) Monoclonal antibodies that recognize lacto-N-fucopentaose III (CD15) react with the adhesion-promoting glycoprotein family (LFA-1/Hmac-1/gp150,95) and CR1 on human neutrophils. J Immunol 139:1631–1639PubMedGoogle Scholar
  20. 20.
    Skubitz KM, Mendiola JR, Collett MS (1988) CD15 monoclonal antibodies with a phosphotyrosine-containing protein on the surface of human neutrophils. J Immunol 141:4318–4323PubMedGoogle Scholar
  21. 21.
    Albrechtsen M, Kerr MA (1989) Characterization of human neutrophil glycoproteins expressing the CD15 differentiation antigen (3-fucosyl-N-acetyllactosamine). British J Haematol 72:312–320Google Scholar
  22. 22.
    Lucka L, Fernando M, Grunow D, Kannicht C, Horst AK, Nollau P, Wagener C (2005) Identification of Lewis x structures of the cell adhesion molecule CEACAM1 from human granulocytes. Glycobiology 15:87–100PubMedCrossRefGoogle Scholar
  23. 23.
    Coombs PJ, Graham SA, Drickamer K, Taylor ME (2005) Selective binding of the scavenger receptor C-type lectin to Lewisx trisaccharide and related glycan ligands. J Biol Chem 280:22993–22999PubMedCrossRefGoogle Scholar
  24. 24.
    Ballaré C, Barrio M, Portela P, Mordoh J (1995) Functional properties of FC-2.15, a monoclonal antibody that mediates human complement cytotoxicity against breast cancer cells. Cancer Immunol Immunother 41:15–22PubMedGoogle Scholar
  25. 25.
    Capurro M, Bover L, Portela P, Livingston P, Mordoh J (1998) FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis X hapten. Cancer Immunol Immunother 45:334–339PubMedCrossRefGoogle Scholar
  26. 26.
    Mordoh J, Silva C, Albarellos M, Bravo AI, Kairiyama C (1995) Phase I clinical trial in cancer patients of a new monoclonal antibody FC-2.15 reacting with tumor proliferating cells. J Immunother 17:151–160CrossRefGoogle Scholar
  27. 27.
    Capurro M, Ballaré C, Bover L, Portela P, Mordoh J (1999) Differential lytic and agglutinating activity of the anti-LewisX monoclonal antibody FC-2.15 on human polymorphonuclear neutrophils and MCF-7 breast tumor cells. In vitro and in vivo study. Cancer Immunol Immunother 48:100–108PubMedCrossRefGoogle Scholar
  28. 28.
    Robinson MK, Andrew D, Rosen H, Brown D, Stephens P, Butcher EC (1992) Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events. J Immunol 148:1080–1085PubMedGoogle Scholar
  29. 29.
    Sánchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2 and LFA-3. Proc Natl Acad Sci USA 79:7489–7493PubMedCrossRefGoogle Scholar
  30. 30.
    Drbal K, Angelisová P, Cerný J, Pavlistova D, Cebecauer M, Novak P, Horejsi V (2000) Human leukocytes contain a large pool of free forms of CD18. Biochem Biophys Res Commun 275:295–299PubMedCrossRefGoogle Scholar
  31. 31.
    Jaffé EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins: identification by morphologic and immunologic criteria. J Clin Invest 52:2745–2756PubMedGoogle Scholar
  32. 32.
    Soule HD, Vazguez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416PubMedGoogle Scholar
  33. 33.
    Kawamura N, Imanishi N, Koike H, Nakahara H, Phillips L, Morooka S (1995) Lipoteichoic acid-induced neutrophil adhesion via E-selectin to human umbilical vein endothelial cells (HUVECs). Biochem Biophys Res Commun 217:1208–1215PubMedCrossRefGoogle Scholar
  34. 34.
    Liao J-W, Kang J-J, Jeng C-R, Chang S-K, Kuo M-J, Wang S-C, Liu MRS, Pang VF (2006) Cartap-induced cytotoxicity in mouse C2C12 myoblast cell line and the roles of calcium ion and oxidative stress on the toxic effects. Toxicology 219:73–84PubMedCrossRefGoogle Scholar
  35. 35.
    Majuri M-L, Pinola M, Niemelä R, Tiisala S, Natunen J, Renkonen O, Renkonen R (1994) α2,3-Sialyl and α1,3-fucosyltransferase-dependent synthesis of sialyl Lewis x, an essential oligosaccharide present on L-selectin counterreceptors, in culture endothelial cells. Eur J Immunol 24:3205–3210PubMedCrossRefGoogle Scholar
  36. 36.
    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-Lex. Science 250:1130–1132PubMedCrossRefGoogle Scholar
  37. 37.
    Buyon JP, Abramson SB, Philips MR, Slade SG, Ross GD, Weissman G, Winchester RJ (1988) Dissociation between increased surface expression of gp165/95 and homotypic neutrophil aggregation. J Immunol 140:3156–3160PubMedGoogle Scholar
  38. 38.
    Bild T, Jose J, Hartmann RW (2004) Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action. Archiv der Pharmazie 337:687–694PubMedCrossRefGoogle Scholar
  39. 39.
    Harris JF, Chin J, Jewett MA, Kennedy M, Gorczynski RM (1984) Monoclonal antibodies against SSEA-1 antigen: binding properties and inhibition of human natural killer cell activity against target cells bearing SSEA-1 antigen. J Immunol 132:2502–2509PubMedGoogle Scholar
  40. 40.
    Magnani JL, Ball ED, Fanger MW, Hakomori S-I, Ginsburg V (1984) Monoclonal antibodies PMN 6, PMN 29, and PM-81 bind differently to glycolipids containing a sugar sequence ocurring in lacto-N-fucopentaose III. Arch Biochem Biophys 233:501–506PubMedCrossRefGoogle Scholar
  41. 41.
    van Roon AM, Pannu NS, de Vrind JP, van der Marel GA, van Boom JH, Hokke CH, Deelder AM, Abrahams JP (2004) Structure of an anti-Lewis X Fab fragment in complex with its Lewis X antigen. Structure 7:1227–1236CrossRefGoogle Scholar
  42. 42.
    Ball ED, Selvaggi K, Hurd D, Herzig R, Clark L, Malley V, Persichetti J, deMagelhaus-Silverman M (1995) Phase I clinical trial of serotherapy in patients with acute myeloid leukemia with an immunoglobulin M monoclonal antibody to CD15. Clin Cancer Res 1:965–972PubMedGoogle Scholar
  43. 43.
    Stocks SC, Kerr MA (1992) Stimulation of neutrophil adhesion by antibodies recognizing CD15 (Lex) and CD15-expressing carcinoembryonic antigen-related glycoprotein NCA-160. Biochem J 288:23–27PubMedGoogle Scholar
  44. 44.
    Wong IHN, Lau WY, Leung T, Yeo W, Johnson PJ (1999) Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma: a quantitative analysis. Clin Can Res 5:4021–4027Google Scholar
  45. 45.
    Yamashita JI, Kurusu Y, Fujino N, Saisyoji T, Ogawa M (2000) Detection of circulating tumor cells in patients with non-small cell lung cancer undergoing lobectomy by video-assisted thoracic surgery: a potential hazard for intraoperative hematogenous tumor cell dissemination. J␣Thorac Cardiovasc Surg 119:899–905PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • María Teresa Elola
    • 1
  • Mariana Isabel Capurro
    • 2
  • María Marcela Barrio
    • 3
  • Peter J. Coombs
    • 4
  • Maureen E. Taylor
    • 4
  • Kurt Drickamer
    • 4
  • José Mordoh
    • 1
    • 3
  1. 1.Fundación Instituto LeloirBuenos AiresArgentina
  2. 2.Division of Molecular and Cell Biology, Sunnybrook and Women’s College Health Sciences Center and Department of Medical BiophysicsUniversity of TorontoOntarioCanada
  3. 3.Centro de Investigaciones Oncológicas – FUCABuenos AiresArgentina
  4. 4.Division of Molecular Biosciences, Biochemistry BuildingImperial CollegeLondon United Kingdom

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