Authors: Masa Bosnjak Lara Prosen Tanja Dolinsek Tanja Blagus Bostjan Markelc Maja Cemazar Celine Bouquet Gregor Sersa
Publish Date: 2013/05/07
Volume: 246, Issue: 11, Pages: 803-819
Abstract
The data on the biological responsiveness of melanoma and endothelial cells that are targeted by Antiangiogenic MEtargidin Peptide AMEP are limited therefore the antiproliferative antimetastatic and antiangiogenic effects of AMEP were investigated in murine melanoma and human endothelial cells after plasmid AMEP gene electrotransfer into the cells in vitro Plasmid AMEP a plasmid coding for the disintegrin domain of metargidin targeting specific integrins had cytotoxic and antiproliferative effects on murine melanoma and human endothelial cells Among the metastatic properties of cells migration invasion and adhesion were investigated Plasmid AMEP strongly affected the migration of murine melanoma and human endothelial cell lines and also affected the invasion of highly metastatic murine melanoma B16F10 and human endothelial cell lines There was no effect on cell adhesion on MatrigelTM or fibronectin in all cell lines The antiangiogenic effect was shown with tube formation assay where human microvascular endothelial cell line HMEC1 proved to be more sensitive to plasmid AMEP gene electrotransfer than the human umbilical vein endothelial cell line HUVEC The study indicates that antiproliferative and antimetastatic biological responses to gene electrotransfer of plasmid AMEP in murine melanoma cells were dependent on the integrin quantity on melanoma cells and not on the expression level of AMEP The strong antiangiogenic effect expressed in human endothelial cell lines was only partly dependent on the quantity of integrins and seemed to be plasmid AMEP dose dependentThe authors acknowledge the financial support from the state budget by the Slovenian Research Agency program no P30003 project no J34211 The research was conducted in the scope of LEA EBAM French–Slovenian European Associated Laboratory Pulsed Electric Fields Applications in Biology and Medicine and COST Action TD1104 We would like to thank Mira Lavric Institute of Oncology Ljubljana Ljubljana Slovenia for all the valuable work she contributed to this research Céline Bouquet is a stockholder and an employee at BioAlliance Pharma The other authors declare no conflict of interest
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