Horizontal transfer of oncogenes by uptake of apoptotic bodies.
Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes. Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-ras(V12)- and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo. Fluorescence in situ hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.
Bergsmedh
A
A
Cancer Center Karolinska Hospital R8:03, SE 17176, Stockholm, Sweden.
Szeles
A
A
Henriksson
M
M
Bratt
A
A
Folkman
M J
MJ
Spetz
A L
AL
Holmgren
L
L
D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D016259:Genes, myc / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D051381:Rats
D004273:DNA, Neoplasm