Horizontal transfer of tumor DNA to endothelial cells in vivo.
Tumor endothelial cells have long been regarded as genomically stable and therefore less likely to develop resistance to antiangiogenic therapies. However, recent findings have challenged this notion. We have shown that DNA can be transferred between cells through phagocytosis of apoptotic bodies by adjacent viable cells. Propagation of the ingested DNA is prevented by the activation of the p53-p21 pathway. In this study, we examined whether concomitant transfer of tumor DNA with genes that inactivate the p53 pathway could overcome the barrier to tumor DNA propagation. Our results demonstrate that fibroblasts and endothelial cells are capable of acquiring and replicating tumor DNA when the apoptotic tumor cells contain the SV40 large T antigen. Analysis of the tumor stroma of xenotransplanted tumors in severe combined immunodeficient mice revealed that a sub-population of the endothelial cells contained tumor DNA. These cells maintained the ability to form functional vessels in an in vivo assay and concurrently express tumor-encoded and endothelial-specific genes.
Ehnfors
J
J
Department of Oncology & Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
Kost-Alimova
M
M
Persson
N Luna
NL
Bergsmedh
A
A
Castro
J
J
Levchenko-Tegnebratt
T
T
Yang
L
L
Panaretakis
T
T
Holmgren
L
L
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D022761:Gene Transfer, Horizontal; D006801:Humans; D051379:Mice; D010587:Phagocytosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D004273:DNA, Neoplasm; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53