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.

Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

“…5 The level of expression of integrins α v β 3 , α v β 5 , α 5 β 1 , α 6 β 4 , α 4 β 1 and α v β 6 has been found in positive correlation with the ability of cells to migrate. 13 In MDA-MB-231 cells the integrin α v β 5 and α v β 3 are particularly highly expressed. 13 Drugs should not be toxic to healthy cells therefore the effect of Vaa-Dis on migration of cancer cell was evaluated at sub-cytotoxic concentrations of Vaa-Dis.…”

“…13 In MDA-MB-231 cells the integrin α v β 5 and α v β 3 are particularly highly expressed. 13 Drugs should not be toxic to healthy cells therefore the effect of Vaa-Dis on migration of cancer cell was evaluated at sub-cytotoxic concentrations of Vaa-Dis. As evident from the WHA results presented in Suppl.…”

“…13 As one of our main research topics is discovering new substances to oppose breast cancer, the major cause of death in women population worldwide, 14 the possibility that Vaa-Dis also affects the migration of cancer cells directed our subsequent experiments. To this end, resolving the question of whether Vaa-Dis is a heterodimeric Dis or a mixture of two homodimeric Dis was secondary so we did not go further to answer it.…”

Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage

“…Disintegrin sequences were originally identified in some snake venoms and modulate cell migration by disrupting RGDintegrin-dependent cell adhesion (50). Disintegrin sequences are also present in endogenous ligands such as the a disintegrin and metalloprotease (ADAM) family of metalloproteases (51).…”

Medical Science Turns Deadly Substances into Life Saving Ones: Snake Venom as a Treatment Option

“…There are three categories of disintegrins according to their integrin selectivity, namely RGD-disintegrins, MLD-disintegrins, and KTS-disintegrins [14]. Out of these, mostly the RGD-disintegrins have been investigated over the years that result in the synthesis of eptifibatide and tirofiban which are currently being evaluated for the treatment of acute coronary ischaemic syndrome [15].…”