Book of abstract 2008

Gene transfer into solid tumors by electroporation
Suzana Mesojednik1, Darja Pavlin2, Gregor Serša1, Andrej Cör3, Simona Kranjc1, Alenka
Grošel1, Gregor Tevž1, Urška Kamenšek1, Maja Čemažar1
1Institute of Oncology Ljubljana, Dept. of Experimental Oncology, Zaloska 2, SI-1000 Ljubljana,
Slovenia; 2University of Ljubljana, Veterinary Faculty, Cesta v Mestni log 47, SI-1000 Ljubljana, Slovenia;
3University of Ljubljana, Faculty of Medicine, Korytkova 2, SI-1000 Ljubljana, Slovenia
Electrogene transfer of plasmid DNA into tumors is a promising approach for the
treatment of cancer. Feasibility and effectiveness of this method was already demonstrated,
elaborating on pulse parameters and plasmid DNA construction. However, efficient in
vivo use of electroporation for gene transfer into solid tumor types is still limited by low
transfection efficiencies. In order to increase electrogene transfections of solid tumors
some novel strategies considering tumor structural properties have to be found.
To explore the influence of histological properties of different tumor types (B16F1
melanoma, EAT carcinoma, SA-1 fibrosarcoma, LPB fibrosarcoma) on electrogene
transfer, the correlation between cell density, collagen or proteoglycans content and
transfection efficiencies was determined. Further, in order to increase transfection efficiency
of electrogene transfer into tumors, the extracellular matrix of tumors was modulated by
enzymes hyaluronidase or/and collagenase before electrotransfection.
Our results demonstrate that soft tumors with spherical and larger cell size, low
proteoglycans and collagen content and low cell density are more effectively transfected
(B16F1, EAT) than more rigid tumors with high proteoglycans and collagen content,
small and spindle-shaped cells and high cell density (LPB and SA-1). Modulation of
extracellular components with enzymes collagenase and hyaluronidase can increase
electrogene delivery into rigid tumor types such as fibrosarcomas. The highest transfection
efficiencies were obtained when combination of enzymes were used.
In conclusion, our study demonstrates that knowledge about histological properties of
p28
tumors is important for development of of novel strategies to deliver sufficient amounts of
plasmid DNA to the tumor cells by electroporation. Namely, electrogene transfer might be
improved by modulation of tumor extracellular matrix with enzymes such as collagenase
and hyaluronidase.
110