The effect of the histological properties of tumors on transfection efficiency of electrically assisted gene delivery to solid tumors in mice.
Uniform DNA distribution in tumors is a prerequisite step for high transfection efficiency in solid tumors. To improve the transfection efficiency of electrically assisted gene delivery to solid tumors in vivo, we explored how tumor histological properties affected transfection efficiency. In four different tumor types (B16F1, EAT, SA-1 and LPB), proteoglycan and collagen content was morphometrically analyzed, and cell size and cell density were determined in paraffin-embedded tumor sections under a transmission microscope. To demonstrate the influence of the histological properties of solid tumors on electrically assisted gene delivery, the correlation between histological properties and transfection efficiency with regard to the time interval between DNA injection and electroporation was determined. Our data demonstrate that soft tumors with larger spherical cells, low proteoglycan and collagen content, and low cell density are more effectively transfected (B16F1 and EAT) than rigid tumors with high proteoglycan and collagen content, small spindle-shaped cells and high cell density (LPB and SA-1). Furthermore, an optimal time interval for increased transfection exists only in soft tumors, this being in the range of 5-15 min. Therefore, knowledge about the histology of tumors is important in planning electrogene therapy with respect to the time interval between DNA injection and electroporation.
Mesojednik
S
S
Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, Slovenia.
Pavlin
D
D
Sersa
G
G
Coer
A
A
Kranjc
S
S
Grosel
A
A
Tevz
G
G
Cemazar
M
M
D000818:Animals; D002277:Carcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002452:Cell Count; D045744:Cell Line, Tumor; D048429:Cell Size; D003094:Collagen / Q000032:analysis; D004247:DNA / Q000008:administration & dosage*; D018274:Electroporation; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007267:Injections; D008156:Luciferases / Q000235:genetics; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D009336:Necrosis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011509:Proteoglycans / Q000032:analysis; D011897:Random Allocation; D012509:Sarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D014162:Transfection / Q000379:methods
D011509:Proteoglycans; D049452:Green Fluorescent Proteins; D003094:Collagen; D004247:DNA; D008156:Luciferases