Preferences help
enabled [disable] Abstract
Number of results
2010 | 57 | 1 | 55-61
Article title

Effect of α3β1 and αvβ3 integrin glycosylation on interaction of melanoma cells with vitronectin

Title variants
Languages of publication
The metastatic transformation of melanocytes is associated with altered expression of adhesion molecules, including αvβ3 and α3β1 integrins. Integrin αvβ3 is a primary vitronectin (VN) receptor, while both integrin types take part in adhesion to VN when they are in complex with uPAR. Although their role in melanoma cell interaction with VN is of great interest, the influence of N-oligosaccharides attached to these glycoproteins is still unappreciated. The present study assesses the role of αvβ3 and α3β1 integrins and the influence of their glycosylation status on WM9 and WM239 metastatic melanoma cell interactions with VN. Cell adhesion to and migration on VN were selected as the studied cell behaviour parameters. Functionblocking antibodies and swainsonine (SW) treatment were used in these tests. Both cell lines interacted with VN in an integrin-mediated but cell-line-specific manner. In WM9 cells, migration was not completely inhibited by antibodies against α3β1 or αvβ3 integrins, suggesting the participation of other VN receptors. In both cell lines in coprecipitation test the formation of an integrins/uPAR complex was shown. In the presence of SW formation of the complex did not occur, suggesting the participation of glycosylation in this proccess. Additionally, the adhesion properties of WM9 cells were changed after SW treatment. Our results suggest that in these two metastatic cell lines integrin-linked N-oligosaccharides influence the VN adhesion receptor activity and function.
Physical description
  • Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland
  • Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland
  • Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland
  • Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland
  • Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Kraków, Poland
  • Aznavoorian S, Stracke ML, Parson J, McClanahan J, Liotta LA (1996) Integrin αvβ3 mediates chemotactic and haptotactic motility in human melanoma cells through different signaling pathways. J Biol Chem 271: 3247-3254.
  • Baroni A, Paoletti I, Silvestri I, Buommino E, Carriero MV (2003) Early vitronectin receptor downregulation in a melanoma cell line during all-trans retinoic acid-induced apoptosis. Br J Dermatol 148: 424-433.
  • Bellis SL (2004) Variant glycosylation: an underappreciated regulatory mechanism for β1 integrins. Biochim Biophys Acta 1663: 52-60.
  • Besch R, Berking C, Kammerbauer C, Degitz K (2007) Inhibition of urokinase-type plasminogen activator receptor induces apoptosis in melanoma cells by activation of p53. Cell Death Differ 14: 818-829.
  • Blasi F (1999) Proteolysis, cell adhesion, chemotaxis, and invasiveness are regulated by the u-PA-u-PAR-PAI-1 system. Thromb Haemost 82: 298-304.
  • Boukerche H, Baril P, Tabone E, Berard F, Sanhadji K, Balme B, Wolf F, Perrot H, Thomas L (2000) A new Mr 55,000 surface protein implicated in melanoma progression: association with a metastatic phenotype. Cancer Res 60: 5848-5856.
  • Chakraborty AK, Pawelek JM (2003) Gn T-V macrophage and cancer metastasis: A common link. Clin Exp Metastasis 20: 365-373.
  • Chaurasia P, Aguirre-Ghiso JA, Liang OD, Gardsvoll H, Ploug M, Ossowski L (2006) A region in urokinase plasminogen receptor domain III controlling a functional association with α5β1 integrin and tumor growth. J Biol Chem 281: 14852-14863.
  • Ciołczyk-Wierzbicka D, Amoresano A, Casbarra A, Hoja-Łukowicz D, Lityńska A, Laidler P (2004) The structure of the oligosaccharides of N-cadherin from human melanoma cell lines. Glycoconj J 20: 483-492.
  • Degryse B, Resnati M, Czekay R-P, Loskutoff DJ, Blasi F (2005) Domain 2 of the urokinase receptor contains an integrin-interacting epitope with intrinsic signaling activity: generation of a new integrin inhibitor. J Biol Chem 280: 24792-24803.
  • Dorling PR, Huxtable CR, Colegate SM (1980) Inhibition of lysosomal α-mannosidase by swainsonine, an indolizidine alkaloid isolated from Swainsona canescens. Biochem J 191: 649-651.
  • Eliceiri BP, Cheresh DA (2000) Role of α integrins during angiogenesis. Cancer J 6 (Suppl 3): S245-S249.
  • Felding-Habermann B, Fransvea E, O'Toole TEO, Manzuk L, Faha B, Hensler M (2002) Involvement of tumor cell integrin αvβ3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis 19: 427-436.
  • Fogel M, Mechtersheimer S, Huszar M, Smirnov A, Abu-Dahi A, Tilgen W, Reichrath J, Georg T, Altevogt P, Gutwein P (2003) L1 adhesion molecule (CD171) in development and progression of human malignant melanoma. Cancer Lett 189: 237-247.
  • Gellert GC, Goldfarb RH, Kitson RP (2004) Physical association of uPAR with the αv integrin on the surface of human NK cells. Biochem Biophys Res Commun 315: 1025-1032.
  • Gu J, Taniguchi N (2004) Regulation of integrin functions by N-glycans. Glycoconj J 21: 9-15.
  • Guo HB, Liu F, Zhao JH, Chen HL (2000) Down-regulation of acetylglucosaminyltransferase V by tumorigenesis- or metastasis-suppressor gene and its relation to metastatic potential of human hepatocarcinoma cells. J Cell Biochem 79: 370-385.
  • Guo HB, Lee I, Kamar M, Akiyama SK, Pierce M (2002) Aberrant N-glycosylation of β1 integrin causes reduced α5β1 integrin clustering and stimulates cell migration. Cancer Res 62: 6837-6845.
  • Haass NK, Smalley KSM, Li L, Herlyn M (2005) Adhesion, migration and communication in melanocytes and melanoma. Pigment Cell Res 18: 150-159.
  • Hall DE (1999) Vitronectin. In: Extracellular matrix, anchor, and adhesion proteins. Kreis T, Vale R, eds, pp 496-498. A Sambrook & Tooze Publication, Oxford University Press.
  • Hakomori S (2002) Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA 99: 10231-10233.
  • Hapke S, Gawaz M, Dehne K, Köhler J, Marschall JF, Graeff H, Schmitt M, Reuning V, Lengyel E (2001) β3A-Integrin downregulates the urokinase-type plasminogen activator receptor (uPAR) through a PEA 3/ets transcriptional silencing element in the uPAR promoter. Mol Cell Biol 21: 2118-2132.
  • Hodivala-Dilke KM, DiPersio CM, Kreidberg JA, Hynes RO (1998) Novel roles for α3β1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes. J Cell Biol 142: 1357-1369.
  • Horton MA (1997) The αvβ3 integrin 'vitronectin receptor'. Int J Biochem Cell Biol 29: 721-725.
  • Humphries JD, Byron A, Humphries MJ (2008) Integrin ligands at a glance. J Cell Sci 119: 3901-3903.
  • Jin H, Varner J (2004) Integrins: role in cancer development and as treatment targets. Br J Cancer 90: 561-565.
  • Kaltner H, Stierstorfer B (1998) Animal lectins as cell adhesion molecules. Acta Anat (Basel) 161: 162-179.
  • Khatib AM, Nip J, Fallavollita L, Lehmann M, Jensen G, Brodt P (2001) Regulation of urokinase plasminogen activator/plasmin-mediated invasion of melanoma cells by the integrin vitronectin receptor αvβ3. Int J Cancer 91: 300-308.
  • Kremser ME, Przybyło M, Hoja-Łukowicz D, Pocheć E, Amoresano A, Carpentieri A, Bubka M, Lityńska A (2008) Characterisation of α3β1 and αvβ3 integrin N-oligosaccharides in metastatic melanoma WM9 and WM239 cell lines. Biochim Biophys Acta 1780: 1421-1431.
  • Kuphal S, Bauer R, Bosserhoff A-K (2005) Integrin signaling in malignant melanoma. Cancer Metastasis Rev 24: 195-222.
  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.
  • Laidler P, Gil D, Pituch-Noworolska A, Ciołczyk D, Książek D, Przybyło M, Lityńska A (2000) Expression of β1-integrins and N-cadherin in bladder cancer and melanoma cell lines. Acta Biochim Pol 47: 1159-1170.
  • Laidler P, Lityńska A, Hoja-Łukowicz D, Łabędź M, Przybyło M, Ciołczyk-Wierzbicka D, Pocheć E, Trebacz E, Kremser E (2006) Characterization of glycosylation and adherent properties of melanoma cell lines. Cancer Immunol Immunother 55: 112-118.
  • Lityńska A, Pocheć E, Hoja-Łukowicz D, Kremser E, Laidler P, Amoresano A, Monti C (2002) The structure of the oligosaccharides of α3β1 integrin from human ureter epithelium (HCV29) cell line. Acta Biochim Pol 49: 491-500.
  • Lityńska A, Przybyło M, Pocheć E, Kremser E, Hoja-Łukowicz D, Sulowska U (2006) Does glycosylation of melanoma cells influence their interactions with fibronectin? Biochimie 88: 527-534.
  • McKeown-Longo PJ, Panetti TS (1996) Structure and function of vitronectin. Trends Glycosci Glycotechnol 8: 327-340.
  • Melchiori A, Mortarini R, Carlone S, Marchisio PC, Anichini A, Noonan DM, Albini A (1995) The α3β1 integrin is involved in melanoma cell migration and invasion. Exp Cell Res 219: 233-242.
  • Mitjans F, Meyer T, Fittschen C, Goodman S, Jonczyk A, Marshall JF, Reyes G, Piulats J (2000) In vivo therapy of malignant melanoma by means of antagonists of αv integrins. Int J Cancer 87: 716-723.
  • Nadanaka S, Sato C, Kitajima K, Katagiri K, Irie S, Yamagata T (2001) Occurrence of oligosialic acids on integrin α5 subunit and their involvement in cell adhesion to fibronectin. J Biol Chem 276: 33657-33664.
  • Natali PG, Nicotra MR, Filippo F, Bigotti A (1995) Expression of fibronectin, fibronectin isoforms and integrin receptors in melanoma lesions. Br J Cancer 71: 1243-1247.
  • Ochwat D, Hoja-Łukowicz D, Lityńska A (2004) N-glycoproteins bearing β 1-6 branched oligosaccharides from the A375 human melanoma cell line analysed by tandem mass spectrometry. Melanoma Res 14: 479-485.
  • Ono M, Handa K, Withers DA, Hakomori S (2000) Glycosylation effect on membrane domain (GEM) involved in cell adhesion and motility: a preliminary note on functional α3, α5-CD82 glycosylation complex in ldlD 14 cell. Biochem Biophys Res Commun 279: 744-750.
  • Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83: 346-356.
  • Pocheć E, Lityńska A, Amoresano A, Casbarra A (2003) Glycosylation profile of integrin α3β1 changes with melanoma progression. Biochim Biophys Acta 1643: 113-123.
  • Przybyło M, Martuszewska D, Pocheć E, Hoja-Łukowicz D, Lityńska A (2007) Identification of proteins bearing β1-6 branched N-glycans in human melanoma cell lines from different progression stages by tandem mass spectrometry analysis. Biochim Biophys Acta 1770: 1427-1435.
  • Seales EC, Jurado GA, Singhal A, Bellis SL (2003) Ras oncogene directs expression of a differentially sialylated, functionally altered β1 integrin. Oncogene 22: 7137-7145.
  • Seftor REB, Seftor EA, Hendrix MJC (1999) Molecular role(s) for integrins in human melanoma invasion. Cancer Metastasis Rev 18: 359-375.
  • Siddiqui SF, Pawelek J, Handerson T, Lin CY, Dickson RB, Rimm DL, Camp RL (2005) Coexpression of β1,6-N-acetylglucosaminyltransferase V glycoprotein substrates defines aggressive breast cancers with poor outcome. Cancer Epidemiol Biomarkers Prev 14: 2517-2523.
  • Sousa JF, Espreafico EM (2008) Suppression subtractive hybridization profiles of radial growth phase and metastatic melanoma cell lines reveal novel potential targets. BMC Cancer 8: doi:10.1186/1471-2407-8-19.
  • Tarui T, Mazar AP, Cines DB, Takada Y (2001) Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction. J Biol Chem 276: 3983-3990.
  • Tsuji T (2004) Physiological and pathological roles of α3β1 integrin. J Membr Biol 200: 115-132.
  • Tsuji T, Kawada Y, Kai-Murozono M, Komatsu S, Han SA, Takeuchi K, Mizushima H, Miyazaki K, Irimura T (2002) Regulation of melanoma cell migration and invasion by laminin-5 and α3β1 integrin (VLA-3). Clin Exp Metastasis 19: 127-134.
  • Tulsiani DRP, Harris TM, Touster O (1982) Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. J Biol Chem 257: 7936-7939.
  • Wang X, Sun P, Al-Qamari A, Tai T, Kawashima I, Paller AS (2001) Carbohydrate-carbohydrate binding of ganglioside to integrin α5 modulates α5β1 function. J Biol Chem 276: 8436-8444.
  • Wei Y, Waltz DA, Rao N, Drummont RJ, Rosenberg S, Chapman HA (1994) Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Cell Biol 269: 32380-32388.
  • Wei Y, Eble JA, Wang Z, Kreidberg JA, Chapman HA (2001) Urokinase receptors promote β1 integrin function through interaction with integrin α3β1. Mol Biol Cell 12: 2975-2986.
  • Zhang F, Tom CC, Kugler MC, Ching TT, Kreidberg JA, Wei Y, Chapman HA (2003) Distinct ligand binding sites in integrin α3β1 regulate matrix adhesion and cell-cell contact. J Cell Biol 163: 177-188.
  • Zhang Y, Zhao J, Zhang X, Guo H, Liu F, Chen H (2004) Relations of the type and branch of surface N-glycans to cell adhesion, migration and integrin expressions. Mol Cell Biochem 260: 137-146.
  • Zheng M, Hakomori S (2000) Soluble fibronectin interaction with cell surface and extracellular matrix is mediated by carbohydrate to-carbohydrate interaction. Arch Biochem Biophys 374: 93-99.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.