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A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect
Princen, Frederic; Robe, Pierre; Lechanteur, Chantal et al.
1999In Clinical Cancer Research, 5 (11), p. 3639-44
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Abstract :
[en] Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described. In this study, we analyzed the mechanisms of the bystander effect in two cell lines exhibiting different capacities of communication (DHD/K12 and 9L). The 9L cells exhibited a very good bystander effect, which was completely blocked by a long-term inhibitor of GJIC, 18 alpha-glycyrrhetinic acid. DHD/K12 cells exhibited a moderate bystander effect that was not abolished by 18 alpha-glycyrrhetinic acid or 1-octanol, another strong inhibitor of GJIC. Interestingly, we also observed a bystander effect in cultures where HSV-tk-expressing DHD/K12 cells were physically separated from their untransfected counterparts but grown in the same medium. Moreover, the transfer of filtered conditioned medium from GCV-treated HSV-tk-expressing DHD/K12 cells to DHD/K12 parental cells induced a decrease of survival in a concentration-dependent manner, suggesting that the bystander effect in this cell line was mediated by a soluble factor.
Disciplines :
Oncology
Author, co-author :
Princen, Frederic
Robe, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Lechanteur, Chantal ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Mesnil, M.
Rigo, Jean-Marie ;  Université de Liège - ULiège > Département Argenco : Secteur GeMMe > Matériaux non métal. & Procédés d'exécution des construct.
Gielen, Jacques
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Language :
English
Title :
A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect
Publication date :
November 1999
Journal title :
Clinical Cancer Research
ISSN :
1078-0432
eISSN :
1557-3265
Publisher :
American Association for Cancer Research, Inc. (AACR)
Volume :
5
Issue :
11
Pages :
3639-44
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 August 2009

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