title: Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases after intravenous delivery.
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.
authors.affiliation: University Children's Hospital, Ulm D-89075, Germany.
authors.forename: Jiwu
authors.initials: J
authors.lastname: Wei
authors.forename: Sabine
authors.initials: S
authors.lastname: Blum
authors.forename: Marcus
authors.initials: M
authors.lastname: Unger
authors.forename: Gergely
authors.initials: G
authors.lastname: Jarmy
authors.forename: Mathias
authors.initials: M
authors.lastname: Lamparter
authors.forename: Albert
authors.initials: A
authors.lastname: Geishauser
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Vlastos
authors.forename: Gordon
authors.initials: G
authors.lastname: Chan
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Fischer
authors.forename: Dirk
authors.initials: D
authors.lastname: Rattat
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: Christian
authors.initials: C
authors.lastname: Beltinger
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D024201:Bystander Effect; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015687:Cell Hypoxia; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology*; D004730:Endothelium, Vascular / Q000196:embryology* / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism; D018390:Gene Targeting; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D005822:Genetic Vectors; D007275:Injections, Intravenous; D007694:Killer Cells, Natural / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology*; D015996:Survival Rate; D014498:Uracil / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D014498:Uracil; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D043525:Cytosine Deaminase; D005472:Fluorouracil