On the Role of Cell Surface Carbohydrates and their Binding Proteins (lectins) in Tumor Metastasis

This review focuses on the recent advances in investigations of the role of cell surface carbohydrates in tumor metastasis. It also summarizes the results of extensive studies of endogenous lectins, their structure, carbohydrate specificity and biological functions with the major emphasis on the significance of lectin–cell surface carbohydrate interactions in a metastatic process. Numerous data demonstrate that malignant transformation is associated with various and complex alterations in the glycosylation process. Some of these changes might provide a selective advantage for tumor cells during their progression to more invasive and metastatic phenotype. Cell glycosylation depends on the expression and function of various glycosyltransferases and glycosidases. Recently, transfection of genes encoding various glysosyltransferases gene in sense and antisense orientation helped to bring direct evidence that changes in cell surface carbohydrates are important for the metastatic behavior of tumor cells. Cell surface carbohydrates affect tumor cell interactions with normal cells or with the extracellular matrix during metastatic spread and growth. These interactions can be mediated via tumor cell carbohydrates and their binding proteins known as endogenous lectins. The family of the discovered endogenous lectins is rapidly expanding. The number of C-type lectins has reached 50 and at least 10 galectins have been identified. The biological significance of the endogenous lectins and their possible role in tumor growth and metastasis formation has started to unravel. Some lectins recognize the 'foreign' patterns of cell surface carbohydrates expressed by microorganisms and tumor cells, and play a role in innate and adaptive immunity. It was shown that lectins affect tumor cell survival, adhesion to the endothelium or extracellular matrix, as well as tumor vascularization and other processes that are crucial for metastatic spread and growth.

[1]  E. Gorelik Augmentation of the antimetastatic effect of anticoagulant drugs by immunostimulation in mice. , 1987, Cancer research.

[2]  I. Davidsohn,et al.  Loss of isoantigens A, B, and H in carcinoma of the lung. , 1969, The American journal of pathology.

[3]  R. Cummings,et al.  Transfer and expression of a murine UDP-Gal:beta-D-Gal-alpha 1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. Competition reactions between the alpha 1,3-galactosyltransferase and the endogenous alpha 2,3-sialyltransferase. , 1990, The Journal of biological chemistry.

[4]  B. Vandenbunder,et al.  Expression of the transcription factor c-Ets1 correlates with the occurrence of invasive processes during normal and pathological development. , 1994, Invasion & metastasis.

[5]  J. Dennis,et al.  Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. , 1991, Cancer research.

[6]  C. Bucana,et al.  Cell surface properties of B16 melanoma variants with differing metastatic potential. , 1980, Cancer research.

[7]  H. Inohara,et al.  Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. , 1995, Cancer research.

[8]  J. McCoy,et al.  Effects of H-2Kb gene on expression of melanoma-associated antigen and lectin-binding sites on BL6 melanoma cells. , 1991, Cancer research.

[9]  K. Handa,et al.  Histo‐blood group A/B antigen deletion/ reduction vs. continuous expression in human tumor cells as correlated with their malignancy , 1998, International journal of cancer.

[10]  Lin Chen,et al.  The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products , 1998, Oncogene.

[11]  P. Schlesinger,et al.  Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: Characterization and evidence for receptor recycling , 1980, Cell.

[12]  B. Trump,et al.  Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue. , 1985, Cancer Research.

[13]  J. Dennis,et al.  Asn-linked oligosaccharides in lectin-resistant tumor-cell mutants with varying metastatic potential. , 1986, European journal of biochemistry.

[14]  R. Hughes,et al.  Effects of the carbohydrate‐binding protein galectin‐3 on the invasiveness of human breast carcinoma cells , 1996, Journal of cellular physiology.

[15]  J. Dennis,et al.  Characterization of a deficiency in fucose metabolism in lectin-resistant variants of a murine tumor showing altered tumorigenic and metastatic capacities in vivo. , 1981, Cancer research.

[16]  R. Yu,et al.  Alteration of ganglioside composition by stable transfection with antisense vectors against GD3-synthase gene expression. , 1999, Biochemistry.

[17]  H. Inohara,et al.  Bh1 (nwgr) Domain of Bcl-2 Family Galectin-3: a Novel Antiapoptotic Molecule with a Functional Updated Version Citing Articles E-mail Alerts Galectin-3: a Novel Antiapoptotic Molecule with a Functional Bh1 (nwgr) Domain of Bcl-2 Family' , 2022 .

[18]  V. Castronovo,et al.  DECREASED EXPRESSION OF GALECTIN‐3 IS ASSOCIATED WITH PROGRESSION OF HUMAN BREAST CANCER , 1996, The Journal of pathology.

[19]  A. Raz,et al.  Implications of endogenous tumor cell surface lectins as mediators of cellular interactions and lung colonization. , 1986, Cancer research.

[20]  P. Brodt,et al.  Liver in Response to Metastatic Tumor Cells Rapid Induction of Cytokine and E-Selectin Expression in the Updated Version , 1999 .

[21]  E. Gorelik,et al.  Reduction of metastatic properties of BL6 melanoma cells expressing terminal fucose(alpha)1-2-galactose after alpha1,2-fucosyltransferase cDNA transfection. , 1997, Cancer research.

[22]  G. Nicolson,et al.  Malignancies of metastatic murine lymphosarcoma cell lines and clones correlate with decreased cell surface display of RNA tumor virus envelope glycoprotein gp70. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[23]  H. Kagamu,et al.  Purification of L-selectin(low) cells promotes the generation of highly potent CD4 antitumor effector T lymphocytes. , 1998, Journal of immunology.

[24]  R. Kerbel,et al.  Mutagen treatment as a means for selecting immunogenic variants from otherwise poorly immunogenic malignant murine tumors. , 1983, Cancer Research.

[25]  A. Kobata,et al.  Enzymatic basis for the structural changes of asparagine-linked sugar chains of membrane glycoproteins of baby hamster kidney cells induced by polyoma transformation. , 1985, The Journal of biological chemistry.

[26]  Richard D. Cummings,et al.  Galectins: A family of animal β-galactoside-binding lectins , 1994, Cell.

[27]  M. Cohn,et al.  Cytotoxic effects of antigen- and mitogen-induced T cells on various targets. , 1975, Journal of immunology.

[28]  L. A. Murphy,et al.  Carbohydrate binding studies on the Bandeiraea simplicifolia I isolectins. Lectins which are mono-, di-, tri-, and tetravalent for N-acetyl-D-galactosamine. , 1981, The Journal of biological chemistry.

[29]  R. Bast,et al.  Differential expression of the 67-kD laminin receptor and 31-kD human laminin-binding protein in human ovarian carcinomas. , 1994, European journal of cancer.

[30]  S. Barondes,et al.  God must love galectins; he made so many of them. , 1999, Glycobiology.

[31]  G. Lennon,et al.  Molecular cloning of a human genomic region containing the H blood group alpha(1,2)fucosyltransferase gene and two H locus-related DNA restriction fragments. Isolation of a candidate for the human Secretor blood group locus. , 1995, The Journal of biological chemistry.

[32]  A. Raz,et al.  Adhesion of human breast carcinoma to extracellular matrix proteins is modulated by galectin-3. , 1997, Invasion & metastasis.

[33]  U. Galili Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibody. , 1993, Springer seminars in immunopathology.

[34]  A. Raz,et al.  Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. , 1992, Journal of the National Cancer Institute.

[35]  G. Ostrander,et al.  Inhibition of v-fms-induced tumor growth in nude mice by castanospermine. , 1988, Cancer research.

[36]  W. Chaney,et al.  Control of metastasis by Asn-linked, beta1-6 branched oligosaccharides in mouse mammary cancer cells. , 1999, Glycobiology.

[37]  L. Baum,et al.  Apoptosis of T cells mediated by galectin-1 , 1995, Nature.

[38]  K. Pienta,et al.  Galectin-3 induces endothelial cell morphogenesis and angiogenesis. , 2000, The American journal of pathology.

[39]  J. Cancelas,et al.  Enhanced expression of alpha(1,3)-fucosyltransferase genes correlates with E-selectin-mediated adhesion and metastatic potential of human lung adenocarcinoma cells. , 1998, Cancer research.

[40]  M. Monsigny,et al.  Increased alpha2,6 sialylation of N-glycans in a transgenic mouse model of hepatocellular carcinoma. , 1997, Cancer research.

[41]  H. Inohara,et al.  Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion. , 1996, Cancer research.

[42]  M. Taylor,et al.  Biology of animal lectins. , 1993, Annual review of cell biology.

[43]  R. Rogers,et al.  Distribution of murine mannose receptor expression from early embryogenesis through to adulthood , 1998, Cell and Tissue Research.

[44]  R. Brentani,et al.  Asn-linked oligosaccharide-dependent interaction between laminin and gp120/140. An alpha 6/beta 1 integrin. , 1991, The Journal of biological chemistry.

[45]  I. Stamenkovic,et al.  Redirection of tumor metastasis by expression of E-selectin in vivo , 1996, The Journal of experimental medicine.

[46]  J. P. Stone,et al.  P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. , 1993, The Journal of clinical investigation.

[47]  C. Dinarello,et al.  Interleukin 1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1-induced mannose receptors and growth factor production in vitro. , 1996, Journal of the National Cancer Institute.

[48]  D. Kilpatrick Use of lectins as mitogens for lymphocytes. , 1998, Methods in Molecular Medicine.

[49]  F. Vidal-Vanaclocha,et al.  Mannose receptor‐mediated endothelial cell activation contributes to B16 melanoma cell adhesion and metastasis in liver , 1998, Journal of cellular physiology.

[50]  B. Weston,et al.  Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in normal tissues. Alternative splicing, polyadenylation, and isoforms. , 1995, The Journal of biological chemistry.

[51]  P. Gullino,et al.  Angiogenesis can be stimulated or repressed in vivo by a change in GM3:GD3 ganglioside ratio. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[52]  S. Kornfeld,et al.  Structure of Glycoproteins and Their Oligosaccharide Units , 1980 .

[53]  J. Milton,et al.  Lectin methods and protocols , 1997 .

[54]  F. Minni,et al.  Increased CMP-NeuAc:Gal beta 1,4GlcNAc-R alpha 2,6 sialyltransferase activity in human colorectal cancer tissues. , 1989, International journal of cancer.

[55]  A. Raz,et al.  Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. , 1999, Cancer research.

[56]  M. Burger,et al.  Lectin‐resistant variants of mouse melanoma cells. I. Altered metastasizing capacity and tumorigenicity , 1982, International journal of cancer.

[57]  J. Paulson,et al.  Identification of a human neuroectodermal tumor antigen (OFA-I-2) as ganglioside GD2. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Riyao Yang,et al.  Expression of galectin-3 modulates T-cell growth and apoptosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[59]  M. Taylor,et al.  Evolutionary conservation of intron position in a subfamily of genes encoding carbohydrate-recognition domains. , 1991, The Journal of biological chemistry.

[60]  S. Hakomori Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. , 1996, Cancer research.

[61]  G. Pilkington,et al.  Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. , 1996, Cancer letters.

[62]  A. Sahin,et al.  Expression of blood-group antigen A--a favorable prognostic factor in non-small-cell lung cancer. , 1991, The New England journal of medicine.

[63]  R. Wallis,et al.  Impaired Secretion of Rat Mannose-Binding Protein Resulting from Mutations in the Collagen-Like Domain1 , 2000, The Journal of Immunology.

[64]  E. Gorelik,et al.  Control of metastatic properties of BL6 melanoma cells by H-2Kb gene: immunological and nonimmunological mechanisms , 1993, Clinical & Experimental Metastasis.

[65]  V. Diehl,et al.  Gangliotriaosylceramide (asialo GM2), a glycosphingolipid marker for cell lines derived from patients with Hodgkin's disease. , 1983, Journal of Immunology.

[66]  G. Pilkington,et al.  Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. , 1996, Cancer letters.

[67]  W. Weis,et al.  The C‐type lectin superfamily in the immune system , 1998, Immunological reviews.

[68]  A. Passaniti,et al.  Cell surface sialylation and tumor metastasis. Metastatic potential of B16 melanoma variants correlates with their relative numbers of specific penultimate oligosaccharide structures. , 1988, The Journal of biological chemistry.

[69]  H. Lum,et al.  Expression of PKA inhibitor ( PKI) gene abolishes cAMPmediated protection to endothelial barrier dysfunction. , 1999, American journal of physiology. Cell physiology.

[70]  H. Wolf,et al.  The blood group ABO gene transcript is down-regulated in human bladder tumors and growth-stimulated urothelial cell lines. , 1996, Cancer research.

[71]  K. Tanikawa,et al.  Prognostic significance of Lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinomas. , 1996, Gastroenterology.

[72]  G. Tuszynski,et al.  Interaction of the hemostatic and immune systems in the metastatic spread of tumor cells. , 1986, International review of experimental pathology.

[73]  I. Weissman,et al.  Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation , 1994, Cell.

[74]  J. Cusack,et al.  Expression of human alpha(1,3)fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells. , 1999, Cancer research.

[75]  J. Whitsett,et al.  Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. , 1997, Journal of immunology.

[76]  L. Liotta,et al.  Cancer cell invasion and metastasis. , 1992, Scientific American.

[77]  M. Fukuda,et al.  Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression. , 1997, Cancer research.

[78]  Pablo Engel,et al.  The selecting: vascular adhesion molecules , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[79]  M. Mareel,et al.  Biology of cancer invasion and metastasis. , 1992, Acta oto-rhino-laryngologica Belgica.

[80]  J. Cancelas,et al.  Enhanced Expression of α(1,3)-Fucosyltransferase Genes Correlates with E-selectin-mediated Adhesion and Metastatic Potential of Human Lung Adenocarcinoma Cells , 1998 .

[81]  R. Lotan,et al.  Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells. , 1995, Cancer research.

[82]  K. Yamada,et al.  Analysis of the role of glycosylation of the human fibronectin receptor. , 1989, The Journal of biological chemistry.

[83]  T. Sasaki,et al.  Regulatory role of GM3 ganglioside in alpha 5 beta 1 integrin receptor for fibronectin-mediated adhesion of FUA169 cells. , 1993, The Journal of biological chemistry.

[84]  T. Bringman,et al.  Recombinant human β-galactoside binding lectin suppresses clinical and histological signs of experimental autoimmune encephalomyelitis , 1990, Journal of Neuroimmunology.

[85]  V. Hogan,et al.  Evidence for the role of 34‐kDa galactoside‐binding lectin in transformation and metastasis , 1990, International journal of cancer.

[86]  W. Chambers,et al.  Type II integral membrane proteins with characteristics of C-type animal lectins expressed by natural killer (NK) cells. , 1993, Glycobiology.

[87]  J. Arango,et al.  Rous sarcoma virus-transformed baby hamster kidney cells express higher levels of asparagine-linked tri- and tetraantennary glycopeptides containing [GlcNAc-beta (1,6)Man-alpha (1,6)Man] and poly-N-acetyllactosamine sequences than baby hamster kidney cells. , 1986, The Journal of biological chemistry.

[88]  S. Hakomori,et al.  Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. , 1985, Cancer research.

[89]  N. Langkilde,et al.  Expression of histo‐blood‐group‐A/B‐gene‐defined glycosyltransferases in normal and malignant epithelia: Correlation with A/B‐carbohydrate expression , 1992, International journal of cancer.

[90]  K. Sada,et al.  Effect of lectins on protein kinase activity. , 1998, Methods in molecular medicine.

[91]  T. Irimura,et al.  Characterization of human colon carcinoma variant cells selected for sialyl Lex carbohydrate antigen: liver colonization and adhesion to vascular endothelial cells. , 1995, Experimental cell research.

[92]  J. Miyazaki,et al.  Suppression of pulmonary metastasis in murine B16 melanoma cells by transfection of a sialidase cDNA , 1997, International journal of cancer.

[93]  E. Ruoslahti,et al.  A peptide mimic of E-selectin ligand inhibits sialyl Lewis X-dependent lung colonization of tumor cells. , 2000, Cancer research.

[94]  Y. Matsuzawa,et al.  Bisecting N-acetylglucosamine on K562 cells suppresses natural killer cytotoxicity and promotes spleen colonization. , 1996, Cancer research.

[95]  S. Tsuboi,et al.  Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells , 1999, The EMBO journal.

[96]  L. Baum,et al.  Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death , 1998, Journal of Molecular Medicine.

[97]  R. Oriol,et al.  Genetics of ABO, H, Lewis, X and Related Antigens , 1986, Vox sanguinis.

[98]  E. Miyoshi,et al.  Transcriptional Regulation of the N-Acetylglucosaminyltransferase V Gene in Human Bile Duct Carcinoma Cells (HuCC-T1) Is Mediated by Ets-1* , 1996, The Journal of Biological Chemistry.

[99]  T. Irimura,et al.  Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties. , 1981, Cancer research.

[100]  J. Dennis,et al.  Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. , 1988, Cancer research.

[101]  J. Lowe,et al.  A cloned human DNA restriction fragment determines expression of a GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase in transfected cells. Evidence for isolation and transfer of the human H blood group locus. , 1989, The Journal of biological chemistry.

[102]  N. Taniguchi,et al.  Suppression of lung metastasis of B16 mouse melanoma by N-acetylglucosaminyltransferase III gene transfection. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[103]  E. Gorelik,et al.  Mechanisms of Cytotoxic Activity of Lectins , 1994 .

[104]  M. Humphries,et al.  Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[105]  P. Stahl,et al.  The mannose receptor is a pattern recognition receptor involved in host defense. , 1998, Current opinion in immunology.

[106]  Thall Ad,et al.  alpha 1,3-Galactosyltransferase-deficient mice produce naturally occurring cytotoxic anti-Gal antibodies. , 1996 .

[107]  T. Paavonen,et al.  Endothelial and epithelial expression of sialyl Lewisx and sialyl Lewisa in lesions of breast carcinoma , 1997, International journal of cancer.

[108]  J. Dennis,et al.  Different patterns of lectin binding and cell surface sialylation detected on related high- and low-metastatic tumor lines. , 1983, Cancer research.

[109]  G. Rabinovich Galectins: an evolutionarily conserved family of animal lectins with multifunctional properties; a trip from the gene to clinical therapy , 1999, Cell Death and Differentiation.

[110]  K. Titani,et al.  Tissue fibronectin is an endogenous ligand for galectin-1. , 1995, Glycobiology.

[111]  P. Carinci,et al.  Effects of lectins on cytoskeletal organization in Mammalian cells. , 1998, Methods in molecular medicine.

[112]  S. Tsuboi,et al.  Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. , 1994, The Journal of biological chemistry.

[113]  J. Dennis,et al.  Inhibition of N‐linked oligosaccharide processing in tumor cells is associated with enhanced tissue inhibitor of metalloproteinases (TIMP) gene expression , 1993, International journal of cancer.

[114]  H. Cooper,et al.  Elevated expression of H type GDP-L-fucose:beta-D-galactoside alpha-2-L-fucosyltransferase is associated with human colon adenocarcinoma progression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[115]  P. Stanley Surface Carbohydrate Alterations of Mutant Mammalian Cells Selected for Resistance to Plant Lectins , 1980 .

[116]  T. Orntoft Carbohydrate changes in bladder carcinomas. , 1992, APMIS. Supplementum.

[117]  J. Kjaergaard,et al.  Tumor infiltration by adoptively transferred T cells is independent of immunologic specificity but requires down-regulation of L-selectin expression. , 1999, Journal of immunology.

[118]  R. Lotan,et al.  Differential expression of endogenous lectins on the surface of nontumorigenic, tumorigenic, and metastatic cells. , 1986, Cancer research.

[119]  M. Monsigny,et al.  Increased α2,6 Sialylation of N-Glycans in a Transgenic Mouse Model of Hepatocellular Carcinoma , 1997 .

[120]  J. Price,et al.  Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice , 2005, Clinical & Experimental Metastasis.

[121]  N. Sharon,et al.  Lectins as cell recognition molecules. , 1989, Science.

[122]  K. Krishan,et al.  Skeletal muscle metabolism in mice bearing adenocarcinoma. III. Activities of alanine and aspartate aminotransferases. , 1986, Experimental pathology.

[123]  A. Varki,et al.  Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. , 1995, Cancer research.

[124]  F. Minni,et al.  Increased CMP‐NeuAc:Galβ1,4GlcNAc‐R α2,6 sialyltransferase activity in human colorectal cancer tissues , 1989 .

[125]  U. Galili Evolution and pathophysiology of the human natural anti-α-galactosyl IgG (anti-Gal) antibody , 2004, Springer Seminars in Immunopathology.

[126]  J. Dennis,et al.  Oncogenes conferring metastatic potential induce increased branching of Asn-linked oligosaccharides in rat2 fibroblasts. , 1989, Oncogene.

[127]  J. Cusack,et al.  Expression of Human α(1,3)Fucosyltransferase Antisense Sequences Inhibits Selectin-mediated Adhesion and Liver Metastasis of Colon Carcinoma Cells , 1999 .

[128]  R. Yu,et al.  Reduced cell migration, tumor growth and experimental metastasis of rat F‐11 cells whose expression of GD3‐synthase is suppressed , 2000, International journal of cancer.

[129]  W. Kemmner,et al.  Enhanced activity of CMP-NeuAc:Galβ1-4GlcNAc:α2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients , 1993 .

[130]  K. Matsumoto,et al.  Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator. , 1988, Cancer research.

[131]  J. W. Dennis N-linked oligosaccharide processing and tumor cell biology. , 1991, Seminars in cancer biology.

[132]  D. Tweardy,et al.  Lectin-induced apoptosis of tumour cells. , 1993, Glycobiology.

[133]  J. Whitsett,et al.  SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[134]  John L. Wang,et al.  Identification of galectin-3 as a factor in pre-mRNA splicing. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[135]  J. Dennis,et al.  Suppression of tumor growth and metastasis in Mgat5-deficient mice , 2000, Nature Medicine.

[136]  K. Joiner,et al.  The human mannose-binding protein functions as an opsonin , 1989, The Journal of experimental medicine.

[137]  Y. Kozutsumi,et al.  Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: mannan-binding proteindependent cell-mediated cytotoxicity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[138]  L. Old,et al.  GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody , 1982, The Journal of experimental medicine.

[139]  C. Bucana,et al.  Distribution of membrane anionic sites on B16 melanoma variants with differing lung colonising potential , 1980, Nature.

[140]  M. Fukuda Cell Surface Carbohydrates and Cell Development , 1991 .

[141]  L. M. Franks,et al.  Cell surface properties of high‐ and low‐metastatic cell lines selected from a spontaneous mouse lung carcinoma , 1983, International journal of cancer.

[142]  Julie A. Pitcher,et al.  The Role of Sequestration in G Protein-coupled Receptor Resensitization , 1997, The Journal of Biological Chemistry.

[143]  G. Yogeeswaran,et al.  Metastatic potential is positively correlated with cell surface sialylation of cultured murine tumor cell lines. , 1981, Science.

[144]  K. Claffey,et al.  Gangliosides influence angiogenesis in an experimental mouse brain tumor. , 1999, Cancer research.

[145]  V. Laudet,et al.  The c-Ha-ras Oncogene Induces Increased Expression of β-Galactoside α-2,6-Sialyltransferase in Rat Fibroblast (FR3T3) Cells , 1992 .

[146]  A. Kumar,et al.  Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin. , 1997, The Journal of clinical investigation.

[147]  S. Shohet,et al.  Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. , 1988, The Journal of biological chemistry.

[148]  S. Barondes,et al.  Galectins. Structure and function of a large family of animal lectins. , 1994, The Journal of biological chemistry.

[149]  S. Barondes,et al.  Galectins: a family of animal beta-galactoside-binding lectins. , 1994, Cell.

[150]  K. Kayser,et al.  Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from human neutrophils , 1995, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.

[151]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[152]  R. Yu,et al.  Suppression of ganglioside GD3 expression in a rat F-11 tumor cell line reduces tumor growth, angiogenesis, and vascular endothelial growth factor production. , 2000, Cancer research.

[153]  R. Lotan,et al.  Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents. , 1989, Cancer letters.

[154]  K. Olden,et al.  Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy. , 1991, Journal of the National Cancer Institute.

[155]  K. Drickamer Increasing diversity of animal lectin structures. , 1995, Current opinion in structural biology.

[156]  T. Irimura,et al.  Colorectal cancer metastasis determined by carbohydrate-mediated cell adhesion: role of sialyl-LeX antigens. , 1993, Seminars in cancer biology.

[157]  W. Lennarz The Biochemistry of Glycoproteins and Proteoglycans , 1980, Springer US.

[158]  H. Inohara,et al.  Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions , 1994, Glycoconjugate Journal.

[159]  T. Yoshiki,et al.  Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: The importance of surface sialyl Lewisa antigen , 1996, International journal of cancer.

[160]  M. Lipinski,et al.  A glycolipid antigen associated with Burkitt lymphoma defined by a monoclonal antibody. , 1983, Science.

[161]  J. Le Pendu,et al.  Increased tumorigenicity of rat colon carcinoma cells after α1,2‐fucosyltransferase FTA anti‐sense cDNA transfection , 1999, International journal of cancer.

[162]  E. Gorelik,et al.  Role of nk cells in the antimetastatic effect of anticoagulant drugs , 1984, International journal of cancer.

[163]  C. Corless,et al.  Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. , 1997, The American journal of pathology.

[164]  V. Hogan,et al.  Molecular cloning and chromosomal mapping of a human galactoside-binding protein. , 1991, Cancer research.

[165]  K. Hartshorn,et al.  Enhanced Antiviral and Opsonic Activity of a Human Mannose-Binding Lectin and Surfactant Protein D Chimera1 , 2000, The Journal of Immunology.

[166]  M. Taylor,et al.  Orientation of sugars bound to the principal C-type carbohydrate-recognition domain of the macrophage mannose receptor. , 1998, The Biochemical journal.

[167]  M. Burger,et al.  Non-metastasising variants selected from metastasising melanoma cells , 1977, Nature.

[168]  R. Kerbel,et al.  Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. , 1987, Science.

[169]  T. Muramatsu,et al.  Correlation of expression of ABH blood group carbohydrate antigens with metastatic potential in human lung carcinomas , 1993, Cancer.

[170]  S. Frisch,et al.  Disruption of epithelial cell-matrix interactions induces apoptosis , 1994, The Journal of cell biology.

[171]  R. Bresalier,et al.  Metastasis of human colon cancer is altered by modifying expression of the beta-galactoside-binding protein galectin 3. , 1998, Gastroenterology.

[172]  R. Bast,et al.  Expression of the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced human uterine adenocarcinoma. , 1996, Human pathology.

[173]  L. Stoolman Adhesion molecules controlling lymphocyte migration , 1989, Cell.

[174]  J. Le Pendu,et al.  Increase of rat colon carcinoma cells tumorigenicity by alpha(1-2) fucosyltransferase gene transfection. , 1997, Glycobiology.

[175]  J. Lowe,et al.  Molecular cloning of a human fucosyltransferase gene that determines expression of the Lewis x and VIM-2 epitopes but not ELAM-1-dependent cell adhesion. , 1991, The Journal of biological chemistry.

[176]  S. Hakomori,et al.  Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. , 1989, Advances in cancer research.

[177]  A. Raz,et al.  Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis , 2004, Cancer and Metastasis Reviews.

[178]  K. Joiner,et al.  Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella. , 1989, The Journal of clinical investigation.

[179]  R. Lotan,et al.  Expression of galectins in head and neck squamous cell carcinoma , 1996, Head & neck.

[180]  M. Denis,et al.  Evidence for two distinct alpha(1,2)-fucosyltransferase genes differentially expressed throughout the rat colon. , 1994, The Biochemical journal.

[181]  S. Watson,et al.  L-selectin binds to P-selectin glycoprotein ligand-1 on leukocytes: interactions between the lectin, epidermal growth factor, and consensus repeat domains of the selectins determine ligand binding specificity. , 1996, Journal of immunology.

[182]  A. Varki,et al.  Selectin ligands. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[183]  Y. Iwakura,et al.  Growth retardation and early death of β‐1, 4‐galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells , 1997, The EMBO journal.

[184]  R. Bresalier,et al.  Liver endothelial E‐selectin mediates carcinoma cell adhesion and promotes liver metastasis , 1997, International journal of cancer.

[185]  I. Davidsohn,et al.  Isoantigens A, B, and H in benign and malignant lesions of the cervix. , 1969, Archives of pathology.

[186]  T. Irimura,et al.  Carbohydrate chain analysis by lectin binding to electrophoretically separated glycoproteins from murine B16 melanoma sublines of various metastatic properties. , 1984, Cancer research.

[187]  L. Baum,et al.  Galectin-1, an Endogenous Lectin Produced by Thymic Epithelial Cells, Induces Apoptosis of Human Thymocytes , 1997, The Journal of experimental medicine.

[188]  K. Roszkowski,et al.  Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and d-galactose , 2004, Journal of Cancer Research and Clinical Oncology.

[189]  A. Raz,et al.  Induction of tumorigenicity by galectin-3 in a nontumorigenic human breast-carcinoma cell-line. , 1995, International journal of oncology.

[190]  Lin Chen,et al.  Transcriptional Regulation ofN-Acetylglucosaminyltransferase V by the srcOncogene* , 1997, The Journal of Biological Chemistry.

[191]  H. Inohara,et al.  Galectin-3 is a nuclear matrix protein which binds RNA. , 1995, Biochemical and biophysical research communications.

[192]  N Taniguchi,et al.  Overexpression of alpha1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splenic injection in athymic mice. , 1999, Cancer research.

[193]  G. Lennon,et al.  Sequence and expression of a candidate for the human Secretor blood group alpha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. , 1995, The Journal of biological chemistry.

[194]  S. Hakomori,et al.  Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung. , 1992, The New England journal of medicine.

[195]  T. Bringman,et al.  Recombinant human beta-galactoside binding lectin suppresses clinical and histological signs of experimental autoimmune encephalomyelitis. , 1990, Journal of neuroimmunology.

[196]  M. Fukuda Possible roles of tumor-associated carbohydrate antigens. , 1996, Cancer research.

[197]  P. Paty,et al.  Beta 1-6 branching of N-linked carbohydrate is associated with K-ras mutation in human colon carcinoma cell lines. , 1995, Biochemical and biophysical research communications.

[198]  K. Handa,et al.  Histo-blood group A/B versus H status of human carcinoma cells as correlated with haptotactic cell motility: approach with A and B gene transfection. , 1997, Cancer research.

[199]  A. Varki,et al.  P-selectin deficiency attenuates tumor growth and metastasis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[200]  K. Matsumoto,et al.  Inhibition of experimental metastasis by castanospermine in mice: blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. , 1986, Cancer research.

[201]  Y. Ikeda,et al.  Immunohistochemical expression of Sialyl Tn, Sialyl Lewisa, Sialyl Lewisa−b−, and Sialyl Lewisx in primary tumor and metastatic lymph nodes in human gastric cancer , 1996, Journal of surgical oncology.

[202]  R. Ezekowitz,et al.  Collectins: pattern recognition molecules involved in first line host defense. , 1993, Current opinion in immunology.

[203]  T. Irimura,et al.  Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: clinicopathological and immunohistochemical study. , 1993, Cancer research.

[204]  G. Nicolson,et al.  Selection and in vivo properties of lectin-attachment variants of malignant murine lymphosarcoma cell lines. , 1980, Journal of the National Cancer Institute.

[205]  S. Tsuiki,et al.  Biochemical and immunological studies on two distinct ganglioside-hydrolyzing sialidases from the particulate fraction of rat brain. , 1990, Journal of biochemistry.

[206]  P. Altevogt,et al.  Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation , 1983, The Journal of experimental medicine.

[207]  R. Bresalier,et al.  Expression of the endogenous galactose‐binding protein galectin‐3 correlates with the malignant potential of tumors in the central nervous system , 1997, Cancer.

[208]  T. Kawasaki,et al.  Serum lectin with known structure activates complement through the classical pathway. , 1987, The Journal of biological chemistry.

[209]  R. Cummings,et al.  L-14 lectin recognition of laminin and its promotion of in vitro cell adhesion. , 1993, Archives of biochemistry and biophysics.

[210]  J. Dennis Different metastatic phenotypes in two genetic classes of wheat germ agglutinin-resistant tumor cell mutants. , 1986, Cancer research.

[211]  J. Dennis,et al.  Inhibitors of carbohydrate processing: A new class of anticancer agents. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[212]  C. Ponting,et al.  Concepts and principles of glycobiology , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[213]  K. Olden,et al.  The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer. , 1998, Cancer detection and prevention.

[214]  M. Denis,et al.  H blood group antigen carried by CD44V modulates tumorigenicity of rat colon carcinoma cells. , 1994, Cancer research.

[215]  Y. Chung,et al.  Increased sialyl Lewis A expression and fucosyltransferase activity with acquisition of a high metastatic capacity in a colon cancer cell line. , 1997, British Journal of Cancer.

[216]  U. Galili Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. , 1993, Immunology today.