Stem cells with fused gene expression of cytosine deaminase and interferon-β migrate to human gastric cancer cells and result in synergistic growth inhibition for potential therapeutic use
Identifieur interne : 001592 ( Main/Exploration ); précédent : 001591; suivant : 001593Stem cells with fused gene expression of cytosine deaminase and interferon-β migrate to human gastric cancer cells and result in synergistic growth inhibition for potential therapeutic use
Auteurs : Kyoung-Yoon Kim [Corée du Sud] ; Bo-Rim Yi [Corée du Sud] ; Hye-Rim Lee [Corée du Sud] ; Nam-Hee Kang [Corée du Sud] ; Eui-Bae Jeung [Corée du Sud] ; Seung U. Kim [Canada, Corée du Sud] ; Kyung-Chul Choi [Corée du Sud]Source :
- International Journal of Oncology [ 1019-6439 ] ; 2011.
Abstract
Genetically engineered stem cells (GESTECs) producing suicide enzymes and immunotherapeutic cytokines have therapeutic effects on tumors, and may possibly reduce the side effects of toxic drugs used for treatments. Suicide enzymes can convert non-toxic pro-drugs to toxic metabolites that can reduce tumor growth. Cytosine deaminase (CD) is a suicide enzyme that metabolizes a non-toxic pro-drug, 5-fluorocytosine (5-FC), into the cytotoxic agent, 5-fluorouracil (5-FU). As an immunotherapeutic agent, human interferon-β (IFN-β) has anticancer effects. In this study, we used modified human neural stem cells (HB1.F3) expressing the
Url:
DOI: 10.3892/ijo.2011.1288
PubMed: 22159640
PubMed Central: 3584621
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stem cells with fused gene expression of cytosine deaminase and interferon-β migrate to human gastric cancer cells and result in synergistic growth inhibition for potential therapeutic use</title><author><name sortKey="Kim, Kyoung Yoon" sort="Kim, Kyoung Yoon" uniqKey="Kim K" first="Kyoung-Yoon" last="Kim">Kyoung-Yoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Hye Rim" sort="Lee, Hye Rim" uniqKey="Lee H" first="Hye-Rim" last="Lee">Hye-Rim Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Nam Hee" sort="Kang, Nam Hee" uniqKey="Kang N" first="Nam-Hee" last="Kang">Nam-Hee Kang</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Jeung, Eui Bae" sort="Jeung, Eui Bae" uniqKey="Jeung E" first="Eui-Bae" last="Jeung">Eui-Bae Jeung</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-ijo-40-04-1097">Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="af3-ijo-40-04-1097">Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chung-Ang University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22159640</idno><idno type="pmc">3584621</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584621</idno><idno type="RBID">PMC:3584621</idno><idno type="doi">10.3892/ijo.2011.1288</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000A08</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A08</idno><idno 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uniqKey="Kim K" first="Kyoung-Yoon" last="Kim">Kyoung-Yoon Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Hye Rim" sort="Lee, Hye Rim" uniqKey="Lee H" first="Hye-Rim" last="Lee">Hye-Rim Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Nam Hee" sort="Kang, Nam Hee" uniqKey="Kang N" first="Nam-Hee" last="Kang">Nam-Hee Kang</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Jeung, Eui Bae" sort="Jeung, Eui Bae" uniqKey="Jeung E" first="Eui-Bae" last="Jeung">Eui-Bae Jeung</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-ijo-40-04-1097">Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="af3-ijo-40-04-1097">Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Medical Research Institute, Chung-Ang University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement></placeName></affiliation></author><author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name><affiliation wicri:level="1"><nlm:aff id="af1-ijo-40-04-1097">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk</wicri:regionArea><wicri:noRegion>Chungbuk</wicri:noRegion></affiliation></author></analytic><series><title level="j">International Journal of Oncology</title><idno type="ISSN">1019-6439</idno><idno type="eISSN">1791-2423</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Genetically engineered stem cells (GESTECs) producing suicide enzymes and immunotherapeutic cytokines have therapeutic effects on tumors, and may possibly reduce the side effects of toxic drugs used for treatments. Suicide enzymes can convert non-toxic pro-drugs to toxic metabolites that can reduce tumor growth. Cytosine deaminase (CD) is a suicide enzyme that metabolizes a non-toxic pro-drug, 5-fluorocytosine (5-FC), into the cytotoxic agent, 5-fluorouracil (5-FU). As an immunotherapeutic agent, human interferon-β (IFN-β) has anticancer effects. In this study, we used modified human neural stem cells (HB1.F3) expressing the <italic>Escherichia coli</italic> (<italic>E. coli</italic>) CD gene (HB1.F3.CD) or both the CD and human IFN-β genes (HB1.F3.CD.IFN-β) and evaluated their effectiveness on gastric carcinoma cells (AGS); migration of GESTECs to AGS was analyzed as well as formation of 5-FU and IFN-β. Reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm the expression of CD and IFN-β genes in GESTECs along with confirming the production of chemoattractant molecules such as stem cell factor (SCF), CXCR4, c-Kit, vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2). In addition, by co-culturing GESTECs with AGS in the presence of 5-FC, we were able to confirm that cancer growth was inhibited, along with a synergistic effect when the CD and IFN-β genes (HB1.F3.CD.IFN-β) were co-expressed. Indeed a marked anticancer effect was demonstrated when the CD and IFN-β genes were expressed together compared to expression of the CD gene alone (HB1.F3.CD). According to a modified transwell migration assay, the migration of GESTECs toward AGS was confirmed. In conclusion, these data suggest potential application of GESTECs to gastric cancer therapy, due to a remarkable synergistic effect of CD and IFN-β genes in the presence of 5-FC. Additionally, the tumor-selective migration capability <italic>in vitro</italic> suggests that GESTECs are a potential anticancer therapy candidate that may result in minimal side effects compared to the conventional chemotherapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Isik, M" uniqKey="Isik M">M Isik</name></author><author><name sortKey="Caner, S" uniqKey="Caner S">S Caner</name></author><author><name sortKey="Metin Seker, M" uniqKey="Metin Seker M">M Metin Seker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blum, M" uniqKey="Blum M">M Blum</name></author><author><name sortKey="Suzuki, A" uniqKey="Suzuki A">A Suzuki</name></author><author><name sortKey="Ajani, Ja" uniqKey="Ajani J">JA Ajani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fidan, E" uniqKey="Fidan E">E Fidan</name></author><author><name sortKey="Fidan, S" uniqKey="Fidan S">S 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Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boucher, Pd" uniqKey="Boucher P">PD Boucher</name></author><author><name sortKey="Im, Mm" uniqKey="Im M">MM Im</name></author><author><name sortKey="Freytag, So" uniqKey="Freytag S">SO Freytag</name></author><author><name sortKey="Shewach, Ds" uniqKey="Shewach D">DS Shewach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hartmann, Ku" uniqKey="Hartmann K">KU Hartmann</name></author><author><name sortKey="Heidelberger, C" uniqKey="Heidelberger C">C Heidelberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, J" uniqKey="Wei J">J Wei</name></author><author><name sortKey="Wahl, J" uniqKey="Wahl J">J Wahl</name></author><author><name sortKey="Knauss, H" uniqKey="Knauss H">H Knauss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huber, Be" uniqKey="Huber B">BE Huber</name></author><author><name sortKey="Austin, Ea" uniqKey="Austin E">EA Austin</name></author><author><name sortKey="Richards, Ca" uniqKey="Richards C">CA Richards</name></author><author><name sortKey="Davis, St" uniqKey="Davis S">ST Davis</name></author><author><name sortKey="Good, Ss" uniqKey="Good S">SS Good</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saukkonen, K" uniqKey="Saukkonen K">K Saukkonen</name></author><author><name sortKey="Hemminki, A" uniqKey="Hemminki A">A Hemminki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tubiana, M" uniqKey="Tubiana M">M Tubiana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beppu, K" uniqKey="Beppu K">K Beppu</name></author><author><name sortKey="Jaboine, J" uniqKey="Jaboine J">J Jaboine</name></author><author><name sortKey="Merchant, Ms" uniqKey="Merchant M">MS Merchant</name></author><author><name sortKey="Mackall, Cl" uniqKey="Mackall C">CL Mackall</name></author><author><name sortKey="Thiele, Cj" uniqKey="Thiele C">CJ Thiele</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name></author><author><name sortKey="Hui, Am" uniqKey="Hui A">AM Hui</name></author><author><name sortKey="Su, Q" uniqKey="Su Q">Q Su</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakamizo, A" uniqKey="Nakamizo A">A Nakamizo</name></author><author><name sortKey="Marini, F" uniqKey="Marini F">F Marini</name></author><author><name sortKey="Amano, T" uniqKey="Amano T">T Amano</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Corée du Sud</li></country><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Kim, Kyoung Yoon" sort="Kim, Kyoung Yoon" uniqKey="Kim K" first="Kyoung-Yoon" last="Kim">Kyoung-Yoon Kim</name></noRegion><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name><name sortKey="Jeung, Eui Bae" sort="Jeung, Eui Bae" uniqKey="Jeung E" first="Eui-Bae" last="Jeung">Eui-Bae Jeung</name><name sortKey="Kang, Nam Hee" sort="Kang, Nam Hee" uniqKey="Kang N" first="Nam-Hee" last="Kang">Nam-Hee Kang</name><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><name sortKey="Lee, Hye Rim" sort="Lee, Hye Rim" uniqKey="Lee H" first="Hye-Rim" last="Lee">Hye-Rim Lee</name><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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