Author/Authors :
Wei، نويسنده , , Jiwu and Blum، نويسنده , , Sabine and Unger، نويسنده , , Marcus and Jarmy، نويسنده , , Gergely and Lamparter، نويسنده , , Mathias and Geishauser، نويسنده , , Albert and Vlastos، نويسنده , , Georgios A and Chan، نويسنده , , Gordon and Fischer، نويسنده , , Klaus-Dieter and Rattat، نويسنده , , Dirk and Debatin، نويسنده , , Klaus-Michael and Hatzopoulos، نويسنده , , Antonis K and Beltinger، نويسنده , , Christian، نويسنده ,
Abstract :
We show that mouse embryonic endothelial progenitor cells (eEPCs) home preferentially to hypoxic lung metastases when administered intravenously. This specificity is inversely related to the degree of perfusion and vascular density in the metastasis and directly related to local levels of hypoxia and VEGF. Ex vivo expanded eEPCs that were genetically modified with a suicide gene specifically and efficiently eradicated lung metastases with scant patent blood vessels. eEPCs do not express MHC I proteins, are resistant to natural killer cell-mediated cytolysis, and can contribute to tumor vessel formation also in nonsyngeneic mice. These results indicate that eEPCs can be used in an allogeneic setting to treat hypoxic metastases that are known to be resistant to conventional therapeutic regimes.
