Angiostatic activity of the antitumor cytokine interleukin-21

Karolien Castermans, Sebastien P. Tabruyn, Rong Zeng, Judy R. Van Beijnum, Cheryl Eppolito, Warren J. Leonard, Protul A. Shrikant, Arjan W. Griffioen

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4940-4947
Number of pages8
Issue number13
StatePublished - Dec 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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