title: Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effects.
abstract: Recent studies have shown that genetically engineered stem cells (GESTECs) produce suicide enzymes that convert non-toxic pro-drugs to toxic metabolites which selectively migrate toward tumor sites and reduce tumor growth. In the present study, we evaluated whether these GESTECs are capable of migrating to lung cancer cells and examined the potential therapeutic efficacy of gene-directed enzyme pro-drug therapy against lung cancer cells in vitro. A modified transwell migration assay was performed to determine the migratory capacity of GESTECs to lung cancer cells. GESTECs [i.e., HB1.F3.CD or HB1.F3.CD.interferon-β (IFN-β)] engineered to express a suicide gene, cytosine deaminase (CD), selectively migrated toward lung cancer cells. Treatment of a human non-small cell lung carcinoma cell line (A549, a lung carcinoma derived from human lung epithelial cells) with the pro-drug 5-fluorocytosine (5-FC) in the presence of HB1.F3.CD or HB1.F3.CD.IFN-β cells resulted in the inhibition of lung cancer cell growth. Based on the data presented herein, we suggest that GESTECs expressing CD may have a potent advantage for selective treatment of lung cancers. Furthermore, GESTECs expressing fusion genes (i.e., CD and IFN-β) may have a synergic antitumor effect on lung cancer cells.
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Bo-Rim
authors.initials: BR
authors.lastname: Yi
authors.forename: Si-Na
authors.initials: SN
authors.lastname: O
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Kang
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Gang-Joon
authors.initials: GJ
authors.lastname: Heo
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D054443:Cell Migration Assays / Q000379:methods; D002465:Cell Movement / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism; D043525:Cytosine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods; D005437:Flucytosine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: D002630:Chemotactic Factors; D011355:Prodrugs; D016899:Interferon-beta; D005437:Flucytosine; D043525:Cytosine Deaminase; D005472:Fluorouracil