Biophysical and biochemical characterization of selectin-ligand interactions pertinent to metastasis

Susan L. Napier, William D. Hanley, Konstantinos Konstantopoulos

Research output: Contribution to conferencePaperpeer-review

Abstract

Hematogenous metastasis is governed by a succession of cell-cell communications amidst a myriad of physiological and competitive stresses regulating the kinetics of each specific receptor-ligand pair binding. This process is governed first by the shear enhanced interactions with selectins via unknown counter-receptors which mediate cell tethering to blood platelets, leukocytes and the vascular endothelium. Our studies show that variant isoforms of CD44 (CD44v) on LS174T colon carcinoma cells possess P-, L- and E-selectin binding activity. Moreover, the selectin binding determinants on CD44v from LS174T cells are sialofucosylated structures displayed on O-linked glycans, akin to those on P-selectin glycoprotein ligand-1. The biophysical properties of selectin/carcinoma ligand binding were characterized using a cell-free flow-based adhesion assay comparing shear-dependent CD44v vs. CD44s adhesion to E-, P- and L-selectin. Furthermore, these findings were compared with the kinetic parameters of whole LS174T carcinoma cell binding to P- and L-selectin at a single molecule level. Based on these unique kinetic properties, quantitative models are employed to direct the development of carcinoma-targeted microparticles. In vitro studies to test the efficacy of the microparticle system will be performed through the use of cone-and-plate rheometry in shearing a mélange of carcinoma cells, whole blood, and microparticles. This scheme will be extended to in vivo studies in mice testing the effectiveness of the metastatic targeting particles.

Original languageEnglish (US)
Number of pages1
StatePublished - Dec 1 2005
Externally publishedYes
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

ASJC Scopus subject areas

  • Engineering(all)

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