Journal
MATRIX BIOLOGY
Volume 32, Issue 1, Pages 52-62Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2012.11.015
Keywords
cDNA cloning; Cell motility; Integrin; Kunitz-type serine protease inhibitor; Snake venom
Categories
Funding
- MERST (Ministere de l'Enseignement Superieur de la Recherche et de la Technologie)
- INSERM
- ARCUS (Action en Region de Cooperation Universitaire et Scientifique)
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A novel Kunitz-type serine proteinase inhibitor, termed PIVL, was purified to homogeneity from the venom of the Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric polypeptide chain cross-linked by three disulfide linkages with an isotope-averaged molecular mass of 7691.7 Da. The 67-residue full-length PIVL sequence was deduced from a venom gland cDNA clone. Structurally, PIVL is built by a single Kunitz/BPTI-like domain. Functionally, it is able to specifically inhibit trypsin activity. Interestingly, PIVL exhibits an anti-tumor effect and displays integrin inhibitory activity without being cytotoxic. Here we show that PIVL is able to dose-dependently inhibit the adhesion, migration and invasion of human glioblastoma U87 cells. Our results also show that PIVL impairs the function of alpha v beta 3 and to a lesser extent, the activity of alpha v beta 6, alpha v beta 5, alpha 1 beta 1 and alpha 5 beta 1 integrins. Interestingly, we demonstrate that the (41)RGN(43) motif of PIVL is likely responsible for its anti-cancer effect. By using time lapse videomicroscopy, we found that PIVL significantly reduced U87 cells motility and affected cell directionality persistence by 68%. These findings reveal novel pharmacological effects for a Kuni-type serine proteinase inhibitor. (c) 2012 Elsevier B.V. All rights reserved.
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