Modulation of Cellular Adhesion by Glycoengineering

被引:29
作者
Dafik, Laila [2 ]
d'Alarcao, Marc [1 ]
Kumar, Krishna [2 ,3 ]
机构
[1] San Jose State Univ, Dept Chem, San Jose, CA 95192 USA
[2] Tufts Univ, Dept Chem, Medford, MA 02155 USA
[3] Tufts Med Ctr, Ctr Canc, Boston, MA 02110 USA
基金
美国国家科学基金会;
关键词
SIALIC-ACID PRECURSOR; TUMOR-CELLS; GLYCOPROTEINS; GLYCOPEPTIDE; EXPRESSION; INTEGRINS; SURFACES; RESIDUES; VACCINE; DESIGN;
D O I
10.1021/jm100374g
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aberrant glycosylation of lipid and protein molecules on cellular surfaces is responsible for many of the pathophysiological events in tumor progression and metastasis. Sialic acids in particular, are over-expressed on the glycocalyx of malignant tumor cells and sialic acid-mediated cell adhesion is required for metastasis. We report here that replacement of sialic acids on cell surfaces with fluorinated congeners dramatically decreases cell adhesion to E- and P-selectin-coated surfaces. Comparison of adhesion of fluorinated cells with those modified with nonfluorinated analogues suggests that both reduce binding of the modified sialosides to their cognate lectins to a similar extent on a per molecule basis. The overall reduction in cell adhesion results from greater cell surface presentation of the fluorinated congeners. This work suggests an avenue for inhibition of metastasis by administration of small molecules and concomitant noninvasive imaging of tumor cells by F-19 MRI before they are visible by other means.
引用
收藏
页码:4277 / 4284
页数:8
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