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Biological Properties of Melanoma and Endothelial Cells after Plasmid AMEP Gene Electrotransfer Depend on Integrin Quantity on Cells

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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 (HMEC-1) 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 dependent.

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Acknowledgments

The authors acknowledge the financial support from the state budget by the Slovenian Research Agency (program no. P3-0003, project no. J3-4211). 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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Authors and Affiliations

  1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia

    Masa Bosnjak, Tanja Dolinsek, Tanja Blagus, Bostjan Markelc, Maja Cemazar & Gregor Sersa

  2. Kolektor Group, Nanotesla Institute, Stegne 29, 1521, Ljubljana, Slovenia

    Lara Prosen

  3. Faculty of Health Sciences, University of Primorska, Polje 42, 6310, Izola, Slovenia

    Maja Cemazar

  4. BioAlliance Pharma, Boulevard du Général Martial Valin 49, 75015, Paris, France

    Celine Bouquet

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  1. Masa Bosnjak
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  2. Lara Prosen
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  3. Tanja Dolinsek
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  4. Tanja Blagus
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  5. Bostjan Markelc
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  6. Maja Cemazar
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  7. Celine Bouquet
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  8. Gregor Sersa
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Correspondence to Gregor Sersa.

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Bosnjak, M., Prosen, L., Dolinsek, T. et al. Biological Properties of Melanoma and Endothelial Cells after Plasmid AMEP Gene Electrotransfer Depend on Integrin Quantity on Cells. J Membrane Biol 246, 803–819 (2013). https://doi.org/10.1007/s00232-013-9550-y

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  • DOI: https://doi.org/10.1007/s00232-013-9550-y

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