Intermolecular interactions between glycomodules of plant cell wall arabinogalactan-proteins and extensins.

Hydroxyproline-rich glycoproteins (HRGPs) are a unique component of plant cell walls, undergoing extensive posttranslational modification such as proline hydroxylation and hydroxyproline-O-glycosylation. Arabinogalactan proteins (AGPs) and extensins are major members of the HRGP superfamily. AGPs have repetitive AlaHyp, SerHyp, and ThrHyp peptides, the Hyp residues being glycosylated with large type II arabinogalactan polysaccharides, while extensins contain characteristic SerHyp and SerHyp motifs with arabinosylated (1-4 residues) Hyp.

Deformability of breast cancer cells in correlation with surface markers and cell rolling.

Although the cancer stem cell (CSC) hypothesis has been around for many years, the reliability of cell-surface markers to classify CSCs has remained debatable. The finding that cancerous cells are significantly more deformable than healthy ones has provided motivation to consider mechanical properties as a possible biomarker for stemness. In this study, using the micropipette aspiration technique, mechanical properties of multiple breast cancer cell lines were investigated and correlated with breast cancer stem cell (BCSC) marker, CD44/CD24/ALDH1.

CD44 variant isoforms expressed by breast cancer cells are functional E-selectin ligands under flow conditions.

Adhesion of circulating tumor cells to vascular endothelium is mediated by specialized molecules that are functional under shear forces exerted by hematogenous flow. Endothelial E-selectin binding to glycoforms of CD44 mediates shear-resistant cell adhesion in numerous physiological and pathological conditions. However, this pathway is poorly understood in breast cancer and is the focus of the present investigation.

Expression of E-selectin ligands on circulating tumor cells: cross-regulation with cancer stem cell regulatory pathways?

Although significant progress has been made in the fight against cancer, successful treatment strategies have yet to be developed to combat those tumors that have metastasized to distant organs. Poor characterization of the molecular mechanisms of cancer spread is a major impediment to designing predictive diagnostics and effective clinical interventions against late stage disease. In hematogenous metastasis, it is widely suspected that circulating tumor cells (CTCs) express specific adhesion molecules that actively initiate contact with the vascular endothelium lining the vessel walls of the target organ.

HECA-452 is a non-function blocking antibody for isolated sialyl Lewis x adhesion to endothelial expressed E-selectin under flow conditions.

E-selectin, expressed on inflamed endothelium, and sialyl Lewis x (sLe(x)), present on the surface of leukocytes, play a key role in leukocyte-endothelial interactions during leukocyte recruitment to sites of inflammation. HECA-452 is a monoclonal antibody (mAb) that recognizes sLe(x) and is routinely used by investigators from diverse fields who seek to unravel the mechanisms of leukocyte adhesion. The data regarding the ability of HECA-452 to inhibit carbohydrate-mediated leukocyte adhesion to E-selectin remains conflicted, in part due to the presence of a variety of potential E-selectin reactive moieties on leukocytes.

In situ Microrheological Determination of Neutrophil Stiffening Following Adhesion in a Model Capillary.

There has been considerable debate on the relative importance of biochemical stimuli and mechanical deformation in neutrophil adhesion in lung capillaries, a process observed following bacterial infection in the body. In contrast to venules, where the vessel diameter is larger than the leukocyte diameter (6-9 microm) and the adhesion process is better understood, in lung capillaries the vessel diameter (2-8 microm) is smaller than the leukocyte diameter. In this study, a micropipette was used as a model for the alveolar capillary microcirculation, allowing the effects of adhesion molecules (ICAM-1) on cell mechanical properties to be observed while applying a mechanical deformation.

Leukocyte adhesion in capillary-sized, P-selectin-coated micropipettes.

Objective: Leukocyte retention in lung capillaries is observed in normal physiology and following a bacterial infection. It has been hypothesized that cells either become mechanically trapped or adhere to capillary endothelial cells via adhesion molecules. We propose that retention involves both mechanical and adhesive forces and that the biochemical adhesive force is modulated by mechanical forces that alter the area of contact between leukocytes and endothelium.

PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow.

P-selectin glycoprotein ligand-1 (PSGL-1) has been proposed as an important tethering ligand for E-selectin and is expressed at a modest level on human leukocytes. Sialyl Lewis x (sLe(x))-like glycans bind to E-selectin and are expressed at a relatively high level on circulating leukocytes. It is unclear whether PSGL-1 has unique biochemical attributes that contribute to its role as an E-selectin ligand.