Snake venom disintegrins and cell migration

Abstract

Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion.

Keywords: ADAM; cell migration; disintegrin; snake venom; αvβ3 integrin.

Figure 1

A (top) Effects of Disba-01 on the migration of three different cell lines. The cells were plated on the migration inserts in the presence of increasing concentrations of DisBa-01 for 22 h. Migration was expressed as a percentage of the control (100%). Cells were counted with a microscope (ten random fields per experiment). Results represents mean ± standard error of three individual experiments, *** p < 0.0001. B (bottom) Integrin profile of the cells tested in the migration assay using DisBa-01. Fibroblasts (FH) express α_vβ₃, α_vβ₅, α₆, and β₁. MDA-MB-231 breast tumor cells express α_vβ₃, α_vβ₅, α₆, α₂, and β₁. DU-145 prostate tumor cells express more α_vβ₅, α₆, α₂, β₁, and less α_vβ₃ and α₄. The presence of integrin receptors on the cell surface was determined by flow cytometry with FITC-anti-α_vβ₃, α_vβ₅, α₆, α₄, α₂, β₁ and α_v subunit integrin antibodies.