TY - JOUR
T1 - Angiostatic activity of the antitumor cytokine interleukin-21
AU - Castermans, Karolien
AU - Tabruyn, Sebastien P.
AU - Zeng, Rong
AU - Van Beijnum, Judy R.
AU - Eppolito, Cheryl
AU - Leonard, Warren J.
AU - Shrikant, Protul A.
AU - Griffioen, Arjan W.
PY - 2008/12/15
Y1 - 2008/12/15
N2 - Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immuno-therapeutic 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.
AB - Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immuno-therapeutic 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.
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U2 - 10.1182/blood-2007-09-113878
DO - 10.1182/blood-2007-09-113878
M3 - Article
C2 - 18515660
AN - SCOPUS:58149396866
SN - 0006-4971
VL - 112
SP - 4940
EP - 4947
JO - Blood
JF - Blood
IS - 13
ER -