Alternagin-C binding to α2β1 integrin controls matrix metalloprotease-9 and matrix metalloprotease-2 in breast tumor cells and endothelial cells

• DOI: 10.1186/s40409-018-0150-2
• Publication Date: 2018-04-25T09:29:29Z
• Authors: Milene Nóbrega de...; Lívia Mara Santos...; Kelli Cristina Mi...; Ana Carolina Caet...; Patty Karina dos ...; Tamires de Castro...; Heloísa Sobreiro ...
• Keywords: Zymography

Matrix metalloproteinases (MMPs) are key players in tumor progression, helping cells to modify their microenvironment, which allows cell migration secondary sites. The role of integrins, adhesion receptors that connect the extracellular matrix, MMP expression and activity has been previously suggested. However, mechanisms by integrins control not completely understood. Particularly, α2β1 integrin, one major collagen I receptors, studied. Alternagin-C (ALT-C), a glutamate-cysteine-aspartate-disintegrin from Bothrops alternatus venom, high affinity for an integrin. Herein, we used ALT-C as integrin ligand study effect on MMP-9 MMP-2 well cells, fibroblats endothelial migration.ALT-C was purified two steps gel filtration followed anion exchange chromatography. binding properties ALT-C, its dissociation constant (Kd ) relative this (Col I) were determined surface plasmon resonance. effects (10, 40, 100 1000 nM) assays studied using three human lines: fibroblasts, breast line MDA-MB-231, microvascular HMEC-1, considering found microenvironment. analyzed quantitative PCR gelatin zymography, respectively. Focal kinase activation western blotting.Our data demonstrate after acts distinct against depending type: decreases contents activity, but increases focal phosphorylation transmigration; inhibits MMP-2, is necessary angiogenesis. also upregulates c-Myc mRNA level, related suppression.These results controls reveal target development antiangiogenic antimetastatic therapies.