Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases after intravenous delivery.

Wei J, Blum S, Unger M, Jarmy G, Lamparter M, Geishauser A, Vlastos GA, Chan G, Fischer KD, Rattat D, Debatin KM, Hatzopoulos AK, Beltinger C
Cancer Cell. 2004 5 (5): 477-88

PMID: 15144955 · DOI:10.1016/s1535-6108(04)00116-3

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.

MeSH Terms (29)

Animals Bone Neoplasms Bystander Effect Carcinoma, Lewis Lung Cell Hypoxia Cytosine Deaminase Embryonic and Fetal Development Endothelium, Vascular Fluorouracil Genes, Transgenic, Suicide Gene Targeting Genetic Therapy Genetic Vectors Injections, Intravenous Killer Cells, Natural Lung Neoplasms Male Mice Mice, Inbred C3H Mice, Inbred C57BL Neovascularization, Pathologic Osteosarcoma Pentosyltransferases Prodrugs Recombinant Fusion Proteins Stem Cells Survival Rate Uracil Vascular Endothelial Growth Factor A

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