Article (Scientific journals)
Angiostatic activity of the antitumor cytokine interleukin-21.
Castermans, Karolien; Tabruyn, Sébastien; Zeng, Rong et al.
2008In Blood, 112 (13), p. 4940-7
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Keywords :
Angiogenesis Inhibitors/pharmacology; Animals; Antineoplastic Agents; Aorta/cytology; Cell Line; Cell Line, Tumor; Cell Proliferation/drug effects; Chick Embryo; Endothelial Cells/cytology/drug effects; Endothelium, Vascular/cytology; Humans; Interleukins/pharmacology; Mice; Neovascularization, Pathologic/drug therapy; Neovascularization, Physiologic/drug effects; Phosphorylation/drug effects; Receptors, Interleukin-21; STAT3 Transcription Factor/metabolism
Abstract :
[en] Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Castermans, Karolien ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Tabruyn, Sébastien ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Zeng, Rong
van Beijnum, Judy R
Eppolito, Cheryl
Leonard, Warren J
Shrikant, Protul A
Griffioen, Arjan W
Language :
English
Title :
Angiostatic activity of the antitumor cytokine interleukin-21.
Publication date :
2008
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Volume :
112
Issue :
13
Pages :
4940-7
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 November 2010

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