**7. Conclusion**

16 Biomaterials – Physics and Chemistry

The pro-adhesive properties of galectins have been shown several times. But only few efforts have been done to elucidate the potential of galectins as coatings for biomaterial surfaces. In contrast other components of the extracellular matrix are often used. Coatings with peptides from ECM proteins such as RGD or YIGSR peptide are one of the most common methods to modify biomaterial surfaces. Also coatings with complete ECM proteins or specific adhesion proteins have been investigated. Another important molecule class used in biomaterial research today are growth factors (Chan & Mooney, 2008; Shekaran & Garcia, 2011; Straley et al., 2010). The functionalisation with glycans or lectins seems to be underrepresented although their function in natural processes is well known.

Only few studies show the potential of galectins and glycans as biomaterial coatings:

glycan and/or galectin modified materials for improved cell adhesion.

The positive influence of galectins was shown for example as the coating of PLGA scaffolds with recombinant galectin-1 promotes adhesion and growth of immortal rat chondrocytes. Therefore this surface is mentioned to have potential as biomaterial in tissue engineering (Chen et al., 2005). The potential of glycans in biomaterial coatings has also been shown. For example galactose derivatives immobilised on material surfaces were proven to influence the growth and function of liver cells positively. But in this study the receptor molecules and mechanisms of signal transduction were not investigated and binding of an asialoglycoprotein receptor (and not galectin mediated binding) is assumed (De Bartolo et al., 2006). Another study shows combined use of immobilised glycans with galectins as it evidences positive effects of endogenous galectin-1 for adhesion of chondrocytes to a lactose-modified surface (Marcon et al., 2005). These findings prove the possible use of

Fig. 4. Schematic representation of a possible biomaterial set-up using immobilised glycans

as scaffold for subsequent galectin-mediated protein and cell-adhesion

The importance of galectins in cell adhesion and signal transduction has been shown in several investigations. Therefore a possible application of galectins in the assembly of a biomaterial surface mimicking the natural microenvironment seems to be obvious. Anyhow only few articles regarding the use of galectins in biomaterial research have been published. This might be explained by the fact that the fine regulation of galectin mediated cell adhesion and signalling is still not fully understood yet. Therefore it is important to evaluate galectin function under specified conditions to reduce or exclude the risk of unwanted inflammatory or carcinogenic effects.

Taking the presented literature and our own work regarding the biofunctionalisation of surfaces with glycans and galectins together, there is clear evidence that galectins play an important role in cell adhesion and proliferation on specifically functionalised biomaterial surfaces. However, further research has to be done to adopt the fundamental understanding of galectin-glycan mediated cell adhesion processes to an applicable biomaterial surface.

### **8. Acknowledgements**

The authors acknowledge financial support by the DFG (Deutsche Forschungsgemeinschaft) within the Research Training Group 1035 "Biointerface", by the DFG (project EL 135/10-1), and by the excellence initiative of the German federal and state governments through ERS@RWTH Aachen University.

#### **9. References**

Abbott, W. M. & Feizi, T. (1991). Soluble 14-kDa beta-galactoside-specific bovine lectin evidence from mutagenesis and proteolysis that almost the complete polypeptide-

Galectins: Structures, Binding Properties and Function in Cell Adhesion 19

Bohorov, O., Andersson-Sand, H., Hoffmann, J. & Blixt, O. (2006). Arraying glycomics: a

Boura-Halfon, S., Voliovitch, H., Feinstein, R., Paz, K. & Zick, Y. (2003). Extracellular matrix

Brewer, C. F. (2004). Thermodynamic binding studies of galectin-1, -3 and -7. *Glycoconjugate* 

Bruellhoff, K., Fiedler, J., Moller, M., Groll, J. & Brenner, R. E. (2010). Surface coating

Bunkenborg, J., Pilch, B. J., Podtelejnikov, A. V. & Wiśniewski, J. R. (2004). Screening for N-

Cárcamo, C., Pardo, E., Oyanadel, C., Bravo-Zehnder, M., Bull, P., Cáceres, M., Martínez, J.,

lamellipodia in Jurkat T cells. *Experimental Cell Research*, 312, pp. 374-386. Carlsson, S., Oberg, C. T., Carlsson, M. C., Sundin, A., Niisson, U. J., Smith, D., Cummings,

Chan, G. & Mooney, D. J. (2008). New materials for tissue engineering: towards greater control over the biological response. *Trends in Biotechnology*, 26, pp. 382-392. Chen, R., Jiang, X., Sun, D., Han, G., Wang, F., Ye, M., Wang, L. & Zou, H. (2009).

scaffold. *Journal of Biomedical Materials Research Part A*, 93A, pp. 1482-1492. Chenna, R., Sugawara, H., Koike, T., Lopez, R., Gibson, T. J., Higgins, D. G. & Thompson, J.

Cho, M. & Cummings, R. D. (1995). Galectin-1, a beta-galactoside-binding lectin in Chinese

Cho, M. J. & Cummings, R. D. (1997). Galectin-1: Oligomeric structure and interactions with polylactosamine. *Trends in Glycoscience and Glycotechnology*, 9, pp. 47-56. Cooper, D. N. W. (1997). Galectin-1: Secretion and modulation of cell interactions with

Cooper, D. N. W. & Barondes, S. H. (1999). God must love galectins; He made so many of

Cooper, D. N. W. (2002). Galectinomics: finding themes in complexity. *Biochimica et* 

laminin. *Trends in Glycoscience and Glycotechnology*, 9, pp. 57-67.

*Biophysica Acta - General Subjects*, 1572, pp. 209-231.

glycans. *Glycobiology*, 16, pp. 21C-27C.

*Chemistry*, 278, pp. 16397-16404.

*Artificial Organs*, 33, pp. 646-653.

*PROTEOMICS*, 4, pp. 454-465.

*Glycobiology*, 17, pp. 663-676.

*Acids Research*, 31, pp. 3497-3500.

them. *Glycobiology*, 9, pp. 979-984.

*Biological Chemistry*, 270, pp. 5198-5206.

*Journal*, 19, pp. 459-465.

novel bi-functional spacer for one-step microscale derivatization of free reducing

proteins modulate endocytosis of the insulin receptor. *The Journal of Biological* 

strategies to prevent biofilm formation on implant surfaces. *International Journal of* 

glycosylated proteins by liquid chromatography mass spectrometry.

Massardo, L., Jacobelli, S., González, A. & Soza, A. (2006). Galectin-8 binds specific beta1 integrins and induces polarized spreading highlighted by asymmetric

R. D., Almkvist, J., Karlsson, A. & Leffler, H. (2007). Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.

Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. *Journal of Proteome Research*, 8, pp. 651-661. Chen, S. J., Lin, C. C., Tuan, W. C., Tseng, C. S. & Huang, R. N. (2005). Effect of recombinant

galectin-1 on the growth of immortal rat chondrocyte on chitosan-coated PLGA

D. (2003). Multiple sequence alignment with the Clustal series of programs. *Nucleic* 

hamster ovary cells. I. Physical and chemical characterization. *The Journal of* 

chain is necessary for integrity of the carbohydrate recognition domain. *The Journal of Biological Chemistry*, 266, pp. 5552-5557.


Adams, J. C. (2001). Thrombospondins: Multifunctional Regulators of Cell Interactions.

Ahmad, N., Gabius, H. J., Andre, S., Kaltner, H., Sabesan, S., Roy, R., Liu, B. C., Macaluso, F.

Ahmad, N., Gabius, H. J., Sabesan, S., Oscarson, S. & Brewer, C. F. (2004b). Thermodynamic

carbohydrate recognition domain of galectin-3. *Glycobiology*, 14, pp. 817-25. Al-Ansari, S., Zeebregts, C. J., Slart, R., Peppelenbosch, M. & Tio, R. A. (2009). Galectins in atherosclerotic disease. *Trends in Cardiovascular Medicine*, 19, pp. 164-169. Almkvist, J. & Karlsson, A. (2004). Galectins as inflammatory mediators. *Glycoconjugate* 

Appukuttan, P. S. (2002). Terminal alpha-linked galactose rather than *N*-acetyl lactosamine

Arumugham, R. G., Hsieh, T. C., Tanzer, M. L. & Laine, R. A. (1986). Structures of the

Bachhawat-Sikder, K., Thomas, C. J. & Surolia, A. (2001). Thermodynamic analysis of the

Barondes, S. H., Castronovo, V., Cooper, D. N. W., Cummings, R. D., Drickamer, K., Felzi,

Barondes, S. H., Cooper, D. N. W., Gitt, M. A. & Leffler, H. (1994b). Galectins - structure and

Bidon, N., Brichory, F., Bourguet, P., Le Pennec, J. P. & Dazord, L. (2001). Galectin-8: A

Birdsall, B., Feeney, J., Burdett, I. D. J., Bawumia, S., Barboni, E. A. M. & Hughes, R. C.

Blixt, O., Head, S., Mondala, T., Scanlan, C., Huflejt, M. E., Alvarez, R., Bryan, M. C., Fazio,

N- and C-terminal domains. *Biochemistry*, 40, pp. 4859-4866.

*Annual Review of Cell and Developmental Biology*, 17, pp. 25-51.

*Journal of Biological Chemistry*, 279, pp. 10841-10847.

*Journal of Molecular Recognition*, 15, pp. 180-187.

*of Biological Chemistry*, 266, pp. 5552-5557.

*Journal*, 19, pp. 575-581.

*FEBS Letters*, 500, pp. 75-79.

lectins. *Cell*, 76, pp. 597-598.

pp. 20807-20810.

101, pp. 17033-17038.

245-250.

112-126.

chain is necessary for integrity of the carbohydrate recognition domain. *The Journal* 

& Brewer, C. F. (2004a). Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. *The* 

binding studies of bivalent oligosaccharides to galectin-1, galectin-3, and the

is ligand for bovine heart galectin-1 in N-linked oligosaccharides of glycoproteins.

asparagine-linked sugar chains of laminin. *Biochimica et Biophysica Acta*, 883, pp.

binding of galactose and poly-*N*-acetyllactosamine derivatives to human galectin-3.

T., Gitt, M. A., Hirabayashi, J., Hughes, C., Kasai, K.-i., Leffler, H., Liu, F.-T., Lotan, R., Mercurio, A. M., Monsigny, M., Pillai, S., Poirer, F., Raz, A., Rigby, P. W. J., Rini, J. M. & Wang, J. L. (1994a). Galectins: A family of animal -galactoside-binding

function of a large family of animal lectins. *The Journal of Biological Chemistry*, 269,

complex sub-family of galectins. *International Journal of Molecular Medicine*, 8, pp.

(2001). NMR solution studies of hamster galectin-3 and electron microscopic visualization of surface-adsorbed complexes: Evidence for interactions between the

F., Calarese, D., Stevens, J., Razi, N., Stevens, D. J., Skehel, J. J., van Die, I., Burton, D. R., Wilson, I. A., Cummings, R., Bovin, N., Wong, C. H. & Paulson, J. C. (2004). Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. *Proceedings of the National Academy of Sciences of the United States of America*,


Galectins: Structures, Binding Properties and Function in Cell Adhesion 21

Garner, O. B. & Baum, L. G. (2008). Galectin-glycan lattices regulate cell-surface

Giguere, D., Bonin, M. A., Cloutier, P., Patnam, R., St-Pierre, C., Sato, S. & Roy, R. (2008).

Gong, H. C., Honjo, Y., Nangia-Makker, P., Hogan, V., Mazurak, N., Bresalier, R. S. & Raz,

Grafahrend, D., Heffels, K. H., Beer, M. V., Gasteier, P., Moller, M., Boehm, G., Dalton, P. D.

Gu, M., Wang, W., Song, W. K., Cooper, D. N. W. & Kaufman, S. J. (1994). Selective

Guévremont, M., Martel-Pelletier, Boileau, C., Liu, F.-T., Richard, M., Fernandes, J.-C.,

Guex, N. & Peitsch, M. C. (1997). Swiss-Model and the swiss-pdb viewer: an environment for comparative protein modeling. *Electrophoresis*, 18, pp. 2714-2723. Hadari, Y. R., Arbel-Goren, R., Levy, Y., Amsterdam, A., Alon, R., Zakut, R. & Zick, Y.

Hernandez, J. D. & Baum, L. G. (2002). Ah, sweet mystery of death! Galectins and control of

Hirabayashi, J. & Kasai, K. (1991). Effect of amino acid substitution by sited-directed

Hirabayashi, J. & Kasai, K. (1993). The family of metazoan metal-independent beta-

Hirabayashi, J. & Kasai, K. I. (1994). Further evidence by site-directed mutagenesis that

Hirabayashi, J., Hashidate, T., Arata, Y., Nishi, N., Nakamura, T., Hirashima, M., Urashima,

and functions in cancer cells. *Cancer Research*, 59, pp. 6239-6245.

1472-1477.

10, pp. 67-73.

*Diseases*, pp. 636-643.

*Journal of Cell Science*, 113, pp. 2385-2397.

cell fate. *Glycobiology*, 12, pp. 127R-136.

galectin-1. *Glycoconjugate Journal*, 11, pp. 437-442.

*The Journal of Neuroscience*, 24, pp. 1873-1880.

*Glycobiology*, 3, pp. 297-304.

175-181.

*Medicinal Chemistry*, 16, pp. 7811-7823.

glycoprotein organization and signalling. *Biochemical Society Transactions*, 36, pp.

Synthesis of stable and selective inhibitors of human galectins-1 and-3. *Bioorganic &* 

A. (1999). The NH2 terminus of galectin-3 governs cellular compartmentalization

& Groll, J. (2011). Degradable polyester scaffolds with controlled surface chemistry combining minimal protein adsorption with specific bioactivation. *Nature Materials*,

modulation of the interaction of alpha7beta1 integrin with fibronectin and laminin by L-14 lectin during skeletal muscle differentiation. *Journal of Cell Science*, 107, pp.

Pelletier, J.-P. & Reboul, P. (2004). Galectin-3 surface expression on human adult chondrocytes: a potential substrate for collagenase-3. *Annals of the Rheumatic* 

(2000). Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis.

mutagenesis on the carbohydrate recognition and stability of human 14-kDa betagalactoside-binding lectin. *The Journal of Biological Chemistry*, 266, pp. 23648-23653.

galactoside-binding lectins: structure, function and molecular evolution.

conserved hydrophilic residues form a carbohydrate-binding site of human

T., Oka, T., Futai, M., Muller, W. E. G., Yagi, F. & Kasai, K.-i. (2002). Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. *Biochimica et Biophysica Acta - General Subjects*, 1572, pp. 232-254. Horie, H., Kadoya, T., Hikawa, N., Sango, K., Inoue, H., Takeshita, K., Asawa, R., Hiroi, T.,

Sato, M., Yoshioka, T. & Ishikawa, Y. (2004). Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy.


Dam, T. K., Gabius, H. J., Andre, S., Kaltner, H., Lensch, M. & Brewer, C. F. (2005). Galectins

gradient of decreasing binding constants. *Biochemistry*, 44, pp. 12564-12571. Danguy, A., Camby, I. & Kiss, R. (2002). Galectins and cancer. *Biochimica et Biophysica Acta -* 

De Bartolo, L., Morelli, S., Rende, M., Salerno, S., Giorno, L., Lopez, L. C., Favia, P.,

Delgado, V. M. C., Nugnes, L. G., Colombo, L. L., Troncoso, M. F., Fernandez, M. M.,

Dell, A. (2002). Structures of Glycoprotein Glycans. *Australian Journal of Chemistry*, 55, pp. 27-

Demetriou, M., Granovsky, M., Quaggin, S. & Dennis, J. W. (2001). Negative regulation of T-

Di Lella, S., Ma, L., Díaz Ricci, J. C., Rabinovich, G. A., Asher, S. A. & Álvarez, R. M. S.

Di Virgilio, S., Glushka, J., Moremen, K. & Pierce, M. (1999). Enzymatic synthesis of natural

Diehl, C., Engstrom, O., Delaine, T., Hakansson, M., Genheden, S., Modig, K., Leffler, H.,

Do, K.-Y., Smith, D. F. & Cummings, R. D. (1990). LAMP-1 in cho cells is a primary carrier of

Dumic, J., Dabelic, S. & Flogel, M. (2006). Galectin-3: An open-ended story. *Biochimica Et* 

Elola, M. T., Wolfenstein-Todel, C., Troncoso, M. F., Vasta, G. R. & Rabinovich, G. A. (2007).

Furtak, V., Hatcher, F. & Ochieng, J. (2001). Galectin-3 mediates the endocytosis of beta-1

and survival. *Cellular and Molecular Life Sciences*, 64, pp. 1679-1700.

galectin-3. *Journal of the American Chemical Society*, 132, pp. 14577-14589. Diskin, S., Cao, Z. Y., Leffler, H. & Panjwani, N. (2009). The role of integrin glycosylation in

*Journal of Nanoscience and Nanotechnology*, 6, pp. 2344-2353.

galectin-8. *The FASEB Journal*, 25, pp. 242-254.

disaccharide lactose. *Biochemistry*, 48, pp. 786-791.

(Mac-2-antigen). *Glycoconjugate Journal*, 14, pp. 267-274.

*Biophysica Acta-General Subjects*, 1760, pp. 616-635.

*Glycobiology*, 9, pp. 353-364.

*Glycobiology*, 19, pp. 29-37.

*Communications*, 289, pp. 845-850.

*General Subjects*, 1572, pp. 285-293.

37.

739.

bind to the multivalent glycoprotein asialofetuin with enhanced affinities and a

d'Agostino, R. & Drioli, E. (2006). Galactose derivative immobilized glow discharge processed polyethersulfone membranes maintain the liver cell metabolic activity.

Malchiodi, E. L., Frahm, I., Croci, D. O., Compagno, D., Rabinovich, G. A., Wolfenstein-Todel, C. & Elola, M. T. (2011). Modulation of endothelial cell migration and angiogenesis: a novel function for the "tandem-repeat" lectin

cell activation and autoimmunity by Mgat5 N-glycosylation. *Nature*, 409, pp. 733-

(2009). Critical role of the solvent environment in galectin-1 binding to the

and C-13 enriched linear poly-*N*-acetyllactosamines as ligands for galectin-1.

Ryde, U., Nilsson, U. J. & Akke, M. (2010). Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of

galectin-8-mediated trabecular meshwork cell adhesion and spreading.

poly-N-acetyllactosamine chains and is bound preferentially by a mammalian Stype lectin. *Biochemical and Biophysical Research Communications*, 173, pp. 1123-1128. Dong, S. & Hughes, R. C. (1997). Macrophage surface glycoproteins binding to galectin-3

Galectins: matricellular glycan-binding proteins linking cell adhesion, migration,

integrins by breast carcinoma cells. *Biochemical and Biophysical Research* 


Galectins: Structures, Binding Properties and Function in Cell Adhesion 23

Lau, K. S. & Dennis, J. W. (2008). N-Glycans in cancer progression. *Glycobiology*, 18, pp. 750-

Leffler, H., Carlsson, S., Hedlund, M., Qian, Y. & Poirier, F. (2004). Introduction to galectins.

Leppänen, A., Stowell, S., Blixt, O. & Cummings, R. D. (2005). Dimeric galectin-1 binds with

Levy, Y., Ronen, D., Bershadsky, A. D. & Zick, Y. (2003). Sustained induction of ERK,

Levy, Y., Auslender, S., Eisenstein, M., Vidavski, R. R., Ronen, D., Bershadsky, A. D. & Zick,

Liu, F.-T., Patterson, R. J. & Wang, J. L. (2002). Intracellular functions of galectins. *Biochimica* 

Liu, F.-T. (2005). Regulatory Roles of Galectins in the Immune Response. *International* 

Liu, F.-T. & Rabinovich, G. A. (2005). Galectins as modulators of tumour progression. *Nature* 

Liu, T., Qian, W.-J., Gritsenko, M. A., Camp, D. G., Monroe, M. E., Moore, R. J. & Smith, R.

Lobsanov, Y. D., Gitt, M. A., Leffler, H., Barondes, S. H. & Rini, J. M. (1993). X-ray crystal

Marcon, P., Marsich, E., Vetere, A., Mozetic, P., Campa, C., Donati, I., Vittur, F., Gamini, A.

Markowska, A. I., Liu, F. T. & Panjwani, N. (2010). Galectin-3 is an important mediator of

Massa, S. M., Cooper, D. N. W., Leffler, H. & Barondes, S. H. (1993). L-29, an endogenous

Masuda, K., Takahashi, N., Tsukamoto, Y., Honma, H. & Kohri, K. (2000). N-Glycan

and a lactose-modified chitosan. *Biomaterials*, 26, pp. 4975-4984.

A resolution. *The Journal of Biological Chemistry*, 268, pp. 27034-27038. Lopez-Lucendo, M. F., Solis, D., Andre, S., Hirabayashi, J., Kasai, K., Kaltner, H., Gabius, H.

D. (2005). Human Plasma N-Glycoproteome Analysis by Immunoaffinity Subtraction, Hydrazide Chemistry, and Mass Spectrometry. *Journal of Proteome* 

structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-

J. & Romero, A. (2004). Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. *The Journal of Molecular* 

& Paoletti, S. (2005). The role of Galectin-1 in the interaction between chondrocytes

VEGF- and bFGF-mediated angiogenic response. *Journal of Experimental Medicine*,

lectin, binds to glycoconjugate ligands with positive cooperativity. *Biochemistry*, 32,

structures of an osteopontin from human bone. *Biochemical and Biophysical Research* 

high affinity to alpha2,3-sialylated and non-sialylated terminal N-Acetyllactosamine units on surface-bound extended glycans. *The Journal of Biological* 

protein kinase B, and p70 S6 kinase regulates cell spreading and formation of Factin microspikes upon ligation of integrins by galectin-8, a mammalian lectin. *The* 

Y. (2006). It depends on the hinge: a structure-functional analysis of galectin-8, a

760.

*Glycoconjugate Journal*, 19, pp. 433-440.

*Journal of Biological Chemistry*, 278, pp. 14533-14542.

tandem-repeat type lectin. *Glycobiology*, 16, pp. 463-476.

*Archives of Allergy and Immunology*, 136, pp. 385-400.

*et Biophysica Acta (BBA) - General Subjects*, 1572, pp. 263-273.

*Chemistry*, 280, pp. 5549-5562.

*Reviews Cancer*, 5, pp. 29-41.

*Research*, 4, pp. 2070-2080.

*Biology*, 343, pp. 957-970.

207, pp. 1981-1993.

*Communications*, 268, pp. 814-817.

pp. 260-267.


Houzelstein, D., Gonc¸alves, I. R., Fadden, A. J., Sidhu, S. S., Cooper, D. N. W., Drickamer,

Hughes, R. C. (1999). Secretion of the galectin family of mammalian carbohydrate-binding

Ideo, H., Matsuzaka, T., Nonaka, T., Seko, A. & Yamashita, K. (2011). Galectin-8-N-domain

Ilarregui, J. M., Bianco, G. A., Toscano, M. A. & Rabinovich, G. A. (2005). The coming of age

Janik, M. E., Litynska, A. & Vereecken, P. (2010). Cell migration-The role of integrin glycosylation. *Biochimica et Biophysica Acta- General Subjects*, 1800, pp. 545-555. John, C. M., Leffler, H., Kahl-Knutsson, B., Svensson, I. & Jarvis, G. A. (2003). Truncated

Kariya, Y., Kato, R., Itoh, S., Fukuda, T., Shibukawa, Y., Sanzen, N., Sekiguchi, K., Wada, Y.,

Kishishita, S., Nishino, A., Murayama, K., Terada, T., Shirouzu, M. & Yokoyama, S. (2008).

Klyosov, A. A., Zbigniew, J. W. & Platt, D. (2008). *Galectins*. Wiley, ISBN 978-0-470-37318,

Knibbs, R. N., Perini, F. & Goldstein, I. J. (1989). Structure of the Major Concanavalin-a

Knibbs, R. N., Agrwal, N., Wang, J. L. & Goldstein, I. J. (1993). Carbohydrate-binding

Kuwabara, I. & Liu, F. T. (1996). Galectin-3 promotes adhesion of human neutrophils to

Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H.,

saccharides. *The Journal of Biological Chemistry*, 268, pp. 14940-14947. Kubler, D., Hung, C. W., Dam, T. K., Kopitz, J., Andre, S., Kaltner, H., Lohr, M., Manning, J.

*Biochimica et Biophysica Acta- General Subjects*, 1780, pp. 716-722.

laminin. *Journal of Immunology*, 156, pp. 3939-3944.

human breast cancer. *Clinical Cancer Research*, 9, pp. 2374-2383.

Hughes, R. C. (2001). Galectins as modulators of cell adhesion. *Biochimie*, 83, pp. 667-676. Ideo, H., Seko, A., Ishizuka, I. & Yamashita, K. (2003). The N-terminal carbohydrate

family. *Molecular Biology and Evolution*, 21, pp. 1177–1187.

proteins. *Biochimica et Biophysica Acta*, 1473, pp. 172-185.

affinity. *Glycobiology*, 13, pp. 713-723.

*Rheumatic Diseases*, 64, pp. 96-103.

*Biological Chemistry*, 283, pp. 33036-33045.

*Chemistry*, pp.11346-11355

pdb database 2YXS.

*Biochemistry*, 28, pp. 6379-6392.

Hoboken.

2947-2948.

K., Leffler, H. & Poirier, F. (2004). Phylogenetic analysis of the vertebrate galectin

recognition domain of galectin-8 recognizes specific glycosphingolipids with high

recognition mechanism for sialylated and sulfated glycans. *The Journal of Biological* 

of galectins as immunomodulatory agents: impact of these carbohydrate binding proteins in T cell physiology and chronic inflammatory disorders. *Annals of the* 

galectin-3 inhibits tumor growth and metastasis in orthotopic nude mouse model of

Kawasaki, N. & Gu, J. G. (2008). N-Glycosylation of laminin-332 regulates its biological functions: A novel function of the bisecting GlcNAc. *The Journal of* 

Reactive Oligosaccharides of the Extracellular-Matrix Component Laminin.

protein-35 2. Analysis of the interaction of the recombinant polypeptide with

C., He, L. Z., Wang, H., Middelberg, A., Brewer, C. F., Reed, J., Lehmann, W. D. & Gabius, H. J. (2008). Phosphorylated human galectin-3: Facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy.

Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J. & Higgins, D. G. (2007). Clustal W and clustal X version 2.0. *Bioinformatics*, 23, pp.


Galectins: Structures, Binding Properties and Function in Cell Adhesion 25

Ochieng, J., Fridman, R., Nangiamakker, P., Kleiner, D. E., Liotta, L. A., Stetlerstevenson, W.

Ochieng, J., Leite-Browning, M. L. & Warfield, P. (1998b). Regulation of cellular adhesion to

Ozeki, Y., Matsui, T., Yamamoto, Y., Funahashi, M., Hamako, J. & Titani, K. (1995). Tissue fibronectin is an endogenous ligand for galectin-1. *Glycobiology*, 5, pp. 255-261. Pace, K. E., Lee, C., Stewart, P. L. & Baum, L. G. (1999). Restricted receptor segregation into

Patnaik, S. K., Potvin, B., Carlsson, S., Sturm, D., Leffler, H. & Stanley, P. (2006). Complex N-

Paul, J. I. & Hynes, R. O. (1984). Multiple fibronectin subunits and their post-translational modifications. *The Journal of Biological Chemistry*, 259, pp. 13477-13487. Probstmeier, R., Montag, D. & Schachner, M. (1995). Galectin-3, a beta-galactoside-binding

Rabinovich, G. A., Baum, L. G., Tinari, N., Paganelli, R., Natoli, C., Liu, F. T. & Iacobelli, S.

Rabinovich, G. A., Rubinstein, N. & Toscano, M. A. (2002b). Role of galectins in

Rabinovich, G. A., Toscano, M. A., Jackson, S. S. & Vasta, G. R. (2007). Functions of cell

Rabinovich, G. A. & Toscano, M. A. (2009). Turning 'sweet' on immunity: galectin-glycan

Rao, S. P., Wang, Z. Z., Zuberi, R. I., Sikora, L., Bahaie, N. S., Zuraw, B. L., Liu, F. T. &

Rapoport, E. M., Andre, S., Kurmyshkina, O. V., Pochechueva, T. V., Severov, V. V.,

Sakaguchi, M., Shingo, T., Shimazaki, T., Okano, H. J., Shiwa, M., Ishibashi, S., Oguro, H.,

inflammatory response? *Trends in Immunology*, 23, pp. 313-320.

*Biophysica Acta- General Subjects*, 1379, pp. 97-106.

galectin-1. *Journal of Immunology*, 163, pp. 3801-3811.

*Communications*, 246, pp. 788-791.

cells. *Glycobiology*, 16, pp. 305-317.

*General Subjects*, 1572, pp. 274-284.

*Immunology*, 179, pp. 7800-7807.

pp. 2465-2472.

513-520.

pp. 338-352.

pp. 315-324.

G. & Raz, A. (1994). Galectin-3 is a novel substrate for human matrix metalloproteinase-2 and metalloproteinase-9. *Biochemistry*, 33, pp. 14109-14114. Ochieng, J., Green, B., Evans, S., James, O. & Warfield, P. (1998a). Modulation of the

biological functions of galectin-3 by matrix metalloproteinases. *Biochimica et* 

extracellular matrix proteins by galectin-3. *Biochemical and Biophysical Research* 

membrane microdomains occurs on human T cells during apoptosis induced by

glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary

animal lectin, binds to neural recognition molecules. *Journal of Neurochemistry*, 64,

(2002a). Galectins and their ligands: amplifiers, silencers or tuners of the

inflammatory and immunomodulatory processes. *Biochimica et Biophysica Acta-*

surface galectin-glycoprotein lattices. *Current Opinion in Structural Biology*, 17, pp.

interactions in immune tolerance and inflammation. *Nature Reviews Immunology*, 9,

Sriramarao, P. (2007). Galectin-3 functions as an adhesion molecule to support eosinophil rolling and adhesion under conditions of flow. *The Journal of* 

Pazynina, G. V., Gabius, H.-J. & Bovin, N. V. (2008). Galectin-loaded cells as a platform for the profiling of lectin specificity by fluorescent neoglycoconjugates: A case study on galectins-1 and -3 and the impact of assay setting. *Glycobiology*, 18,

Ninomiya, M., Kadoya, T., Horie, H., Shibuya, A., Mizusawa, H., Poirier, F., Nakauchi, H., Sawamoto, K. & Okano, H. (2006). A carbohydrate-binding protein,


Matarrese, P., Fusco, O., Tinari, N., Natoli, C., Liu, F. T., Semeraro, M. L., Malorni, W. &

Mehul, B. & Hughes, R. C. (1997). Plasma membrane targetting, vesicular budding and

Moiseeva, E. P., Spring, E. L., Baron, J. H. & de Bono, D. P. (1999). Galectin 1 modulates

Moiseeva, E. P., Williams, B. & Samani, N. J. (2003). Galectin 1 inhibits incorporation of

Munoz, F. J., Santos, J. I., Arda, A., Andre, S., Gabius, H. J., Sinisterra, J. V., Jimenez-Barbero,

Nangia-Makker, P., Baccarini, S. & Raz, A. (2000a). Carbohydrate-recognition and

Nangia-Makker, P., Honjo, Y., Sarvis, R., Akahani, S., Hogan, V., Pienta, K. J. & Raz, A.

Nangia-Makker, P., Balan, V. & Raz, A. (2008). Regulation of tumor progression by

Nieminen, J., St-Pierre, C. & Sato, S. (2005). Galectin-3 interacts with naive and primed

Nieminen, J., Kuno, A., Hirabayashi, J. & Sato, S. (2008). Visualization of Galectin-3

Nishi, N., Shoji, H., Seki, M., Itoh, A., Miyanaka, H., Yuube, K., Hirashima, M. & Nakamura,

Nishi, N., Itoh, A., Shoji, H., Miyanaka, H. & Nakamura, T. (2006). Galectin-8 and galectin-9

Nishi, N., Abe, A., Iwaki, J., Yoshida, H., Itoh, A., Shoji, H., Kamitori, S., Hirabayashi, J. &

are novel substrates for thrombin. *Glycobiology*, 16, pp. 15C-20C.

long-lasting substitute for galectin-1. *Glycobiology*, pp. 1065-1073.

spectroscopy. *Organic & Biomolecular Chemistry*, 8, pp. 2986-2992.

angiogenesis. *Cancer and Metastasis Reviews*, 19, pp. 51-57.

extracellular Galectin-3. *Cancer Microenvironment*, 1, pp.43-51

*American Journal of Pathology*, 156, pp. 899-909.

alpha M. *Glycobiology*, 13, pp. 755-763.

cell adhesion properties. *International Journal of Cancer*, 85, pp. 545-554. Mazurek, N., Conklin, J., Byrd, J. C., Raz, A. & Bresalier, R. S. (2000). Phosphorylation of the

*Journal of Biological Chemistry*, 275, pp. 36311–36315.

*Journal of Cell Science*, 110, pp. 1169-1178.

*of Vascular Research*, 36, pp. 47-58.

293-300.

1127-1135.

1374–1383.

Iacobelli, S. (2000). Galectin-3 overexpression protects from apoptosis by improving

beta-galactoside-binding protein galectin-3 modulates binding to its ligands. *The* 

release of galectin 3 from the cytoplasm of mammalian cells during secretion.

attachment, spreading and migration of cultured vascular smooth muscle cells via interactions with cellular receptors and components of extracellular matrix. *Journal* 

vitronectin and chondroitin sulfate B into the extracellular matrix of human vascular smooth muscle cells. *Biochimica et Biophysica Acta*, 1619, pp. 125-132. Morris, S., Ahmad, N., Andre, S., Kaltner, H., Gabius, H. J., Brenowitz, M. & Brewer, F.

(2004). Quaternary solution structures of galectins-1, -3, and -7. *Glycobiology*, 14, pp.

J. & Hernaiz, M. J. (2010). Binding studies of adhesion/growth-regulatory galectins with glycoconjugates monitored by surface plasmon resonance and NMR

(2000b). Galectin-3 induces endothetial cell morphogenesis and angiogenesis.

neutrophils, inducing innate immune responses. *Journal of Leukocyte Biology*, 78, pp.

Oligomerization on the Surface of Neutrophils and Endothelial Cells Using Fluorescence Resonance Energy Transfer. *The Journal of Biological Chemistry*, 282, pp.

T. (2003). Galectin-8 modulates neutrophil function via interaction with integrin

Nakamura, T. (2008). Functional and structural bases of a cysteine-less mutant as a


Galectins: Structures, Binding Properties and Function in Cell Adhesion 27

Shekaran, A. & Garcia, A. J. (2011). Extracellular matrix-mimetic adhesive biomaterials for bone repair. *Journal of Biomedical Materials Research Part A*, 96A, pp. 261-272. Shekhar, M. P. V., Nangia-Makker, P., Tait, L., Miller, F. & Raz, A. (2004). Alterations in

Singh, P., Carraher, C. & Schwarzbauer, J. E. (2010). Assembly of fibronectin extracellular

Song, X. Z., Lasanajak, Y., Xia, B. Y., Smith, D. & Cummings, R. (2009a). Fluorescent

Song, X. Z., Xia, B. Y., Stowell, S. R., Lasanajak, Y., Smith, D. F. & Cummings, R. D. (2009b).

Song, X. Z., Lasanajak, Y., Xia, B. Y., Heimburg-Molinaro, J., Rhea, J., Ju, H., Zhao, C. M.,

Sörme, P., Qian, Y. N., Nyholm, P. G., Leffler, H. & Nilsson, U. J. (2002). Low micromolar

Sörme, P., Kahl-Knutsson, B., Huflejt, M., Nilsson, U. J. & Leffler, H. (2004). Fluorescence

Sörme, P., Arnoux, P., Kahl-Knutsson, B., Leffler, H., Rini, J. M. & Nilsson, U. J. (2005).

Stowell, S. R., Arthur, C. M., Mehta, P., Slanina, K. A., Blixt, O., Leffler, H., Smith, D. F. &

Stowell, S. R., Arthur, C. M., Slanina, K. A., Horton, J. R., Smith, D. F. & Cummings, R. D.

Straley, K. S., Foo, C. W. P. & Heilshorn, S. C. (2010). Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries. *Journal of Neurotrauma*, 27, pp. 1-19. Szabo, P., Dam, T. K., Smetana, K., Dvorankova, B., Kurbler, D., Brewer, C. F. & Gabius, H. J.

glycan microarrays. ACS Chemical Biology, vol. 4, no. 9, 741-750.

*American Journal of Pathology*, 165, pp. 1931-1941.

fluorescently tagged glycans. *Glycobiology*, 20, pp. 54.

polysaccharides. *Glycobiology*, 14, pp. 157-67.

*Biological Chemistry*, 283, pp. 20547-20559.

ISBN 1081-0706.

*Chemistry & Biology*, 16, pp. 36-47.

*Chembiochem*, 3, pp. 183-189.

*Biochemistry*, 334, pp. 36-47.

pp. 10109-10123.

galectin-3 expression and distribution correlate with breast cancer progression - Functional analysis of galectin-3 in breast epithelial-endothefial interactions.

matrix. In: *Annual Review of Cell and Developmental Biology*, vol. 26, pp. 397-419,

glycosylamides produced by microscale derivatization of free glycans for natural

Novel fluorescent glycan microarray strategy reveals ligands for galectins.

Molinaro, R., Cummings, R. & Smith, D. (2010). Shotgun glycomics: Functional identification of glycan determinants through a microarray strategy using

inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine.

polarization as an analytical tool to evaluate galectin-ligand interactions. *Analytical* 

Structural and thermodynamic studies on cation-II interactions in lectin-ligand complexes: High-affinity galectin-3 inhibitors through fine-tuning of an argininearene interaction. *Journal of the American Chemical Society*, 127, pp. 1737-1743. Stowell, S. R., Dias-Baruffi, M., Penttila, L., Renkonen, O., Nyame, A. K. & Cummings, R. D.

(2004). Human galectin-1 recognition of poly-N-acetyllactosamine and chimeric

Cummings, R. D. (2008a). Galectin-1,-2, and-3 exhibit differential recognition of sialylated glycans and blood group antigens. *The Journal of Biological Chemistry*, 283,

(2008b). Dimeric galectin-8 induces phosphatidylserine exposure in leukocytes through polylactosamine recognition by the C-terminal domain. *The Journal of* 

(2009). Phosphorylated Human Lectin Galectin-3: Analysis of Ligand Binding by Histochemical Monitoring of Normal/Malignant Squamous Epithelia and by Isothermal Titration Calorimetry. *Anatomia Histologia Embryologia*, 38, pp. 68-75.

Galectin-1, promotes proliferation of adult neural stem cells. *Proceedings of the National Academy of Sciences of the United States of America*, 103, pp. 7112-7117.


Salameh, B. A., Cumpstey, I., Sundin, A., Leffler, H. & Nilsson, U. J. (2010). 1H-1,2,3-Triazol-

Salomonsson, E., Carlsson, M. C., Osla, V., Hendus-Altenburger, R., Kahl-Knutson, B.,

Sano, H., Hsu, D. K., Yu, L., Apgar, J. R., Kuwabara, I., Yamanaka, T., Hirashima, M. & Liu,

Sasaki, T., Brakebusch, C., Engel, J. & Timpl, R. (1998). Mac-2 binding protein is a cell-

Sato, S. & Hughes, R. C. (1992). Binding-specificity of a baby hamster-kidney lectin for H

Sato, S., Ouellet, N., Pelletier, I., Simard, M., Rancourt, A. & Bergeron, M. G. (2002). Role of

Sauerzapfe, B., Krenek, K., Schmiedel, J., Wakarchuk, W. W., Pelantová, H., Kren, V. &

Sebban, L. E., Ronen, D., Levartovsky, D., Elkayam, O., Caspi, D., Aamar, S., Amital, H.,

Seelenmeyer, C., Wegehingel, S., Tews, I., Kunzler, M., Aebi, M. & Nickel, W. (2005). Cell

Seelenmeyer, C., Stegmayer, C. & Nickel, W. (2008). Unconventional secretion of fibroblast

Seetharaman, J., Kanigsberg, A., Slaaby, R., Leffler, H., Barondes, S. H. & Rini, J. R. (1998). X-

2.1-Å resolution. *The Journal of Biological Chemistry*, 273, pp. 13047-13052.

machinery of galectin-1. *The Journal of Cell Biology*, 171, pp. 373-381.

streptococcal pneumonia. *Journal of Immunology*, 168, pp. 1813-1822.

inflammation. *Journal of Immunology*, 179, pp. 1225-1235.

derived vesicles. *FEBS Letters*, 582, pp. 1362-1368.

macrophages. *The Journal of Immunology*, 165, pp. 2156–2164.

*Medicinal Chemistry*, 18, pp. 5367-5378.

35091.

6990.

159.

17, pp. 1606-1613.

Galectin-1, promotes proliferation of adult neural stem cells. *Proceedings of the National Academy of Sciences of the United States of America*, 103, pp. 7112-7117. Sakaguchi, M., Imaizumi, Y., Shingo, T., Tada, H., Hayama, K., Yamada, O., Morishita, T.,

Kadoya, T., Uchiyama, N., Shimazaki, T., Kuno, A., Poirier, F., Hirabayashi, J., Sawamoto, K. & Okano, H. (2010). Regulation of adult neural progenitor cells by Galectin-1/beta 1 Integrin interaction. *Journal of Neurochemistry*, 113, pp. 1516-1524.

1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors. *Bioorganic &* 

Oberg, C. T., Sundin, A., Nilsson, R., Nordberg-Karlsson, E., Nilsson, U. J., Karlsson, A., Rini, J. M. & Leffler, H. (2010). Mutational tuning of galectin-3 specificity and biological function. *The Journal of Biological Chemistry*, 285, pp. 35079-

F.-T. (2000). Human galectin-3 is a novel chemoattractant for monocytes and

adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens and fibronectin. *The EMBO Journal*,

type-I and type-II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. *The Journal of Biological Chemistry*, 267, pp. 6983-

galectin-3 as an adhesion molecule for neutrophil extravasation during

Elling, L. (2009). Chemo-enzymatic synthesis of poly-*N*-acetyllactosamine (poly-LacNAc) structures and their characterization for CGL2-galectin-mediated binding of ECM glycoproteins to biomaterial surfaces. *Glycoconjugate Journal*, 26, pp. 141–

Rubinow, A., Golan, I., Naor, D., Zick, Y. & Golan, I. (2007). The involvement of CD44 and its novel ligand galectin-8 in apoptotic regulation of autoimmune

surface counter receptors are essential components of the unconventional export

growth factor 2 and galectin-1 does not require shedding of plasma membrane-

ray crystal structure of the human galectin-3 carbohydrate recognition domain at


**2** 

*Italy* 

**Biomaterials and Epithesis,** 

G. Fini, L.M. Moricca, A. Leonardi, S. Buonaccorsi and V. Pellacchia

*La Sapienza/ Roma* 

**Our Experience in Maxillo Facial Surgery** 

Maxillofacial prosthetics is considered in literature as ''... the art and science of anatomic, functional and cosmetic reconstruction, by the use of non-living substitutes, of those regions in the maxillae, mandible and face that are missing or defective..." 1. In the maxillofacial surgery where malformative, oncologic traumatologic pathology and the plastic surgery are treated, the maxillofacial prostheses, in selected cases, can reach a satisfactory therapeutic result from functional, aesthetic, psychologic, and social point of views. In a delicate district, such as the face, where a heavy deficit can determine huge psychologic and social problems, the conventional reconstructive surgery intervenes with reconstructive techniques and with the biomaterials insertion, often insufficient to guarantee the restoration of the harmony of the face. When these conditions are verified, the solution resides in the osteointegration concept and in the application of the epithesis. There are certainly some limits of application of these prostheses, first, the ethics limits: the epithesis constitute in fact an alternative only when the conventional reconstructive surgery cannot be applied, but inside these limits, it is really possible to find an excellent therapeutic resource in patients who cannot undergo surgical interventions. In literature, it is possible to find different kinds of reconstruction of missing body parts by the application of prothesis2.The osteointegration concept was introduced at first time by Professor Branemark in 1960 to describe the ''direct structural and functional connection between living bone and the surface of a plant exposed to load, understood as a not static but dynamic process3. According to his school of thought, the technique of positioning of the implant is fundamental, to take place in the most complete precision and to allow the initial stability of one's self. Other elements conditioning the success of the osteointegration are the material of the implant, the form, the areas of the application, and the patient's clinical conditions. The first titanium osteointegration implant was positioned in 1965 in the jaw without dental elements 4;in 1977, implants were positioned in mastoid areas for the application of an acoustic translator. In 1979,implants for the fixation of epithesis of ears, noses, and eyes were positioned. At present, the indication to the position of epithesis as the first choice of treatment is when the conventional reconstructive interventions turn out to be inapplicable or ineffective. The epithesis is a good resolution for the patient because it is not traumatic and has short-time result, removing every psychologic physique obstacle for the inclusion in a normal social life.

**1. Introduction** 

