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 journalArticle

38 Citations (Scopus)

Abstract

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
JournalBlood
Volume112
Issue number13
DOIs
StatePublished - Dec 15 2008
Externally publishedYes

Fingerprint

Cytokines
Endothelial cells
Endothelial Cells
Tumors
Interleukin-2
Interleukin-21 Receptors
Neoplasms
Chorioallantoic Membrane
Interleukin-15
Phosphorylation
interleukin-21
Chick Embryo
Interleukin-4
Animals
Animal Models
Genes
Membranes
Research
Experiments
In Vitro Techniques

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Castermans, K., Tabruyn, S. P., Zeng, R., Van Beijnum, J. R., Eppolito, C., Leonard, W. J., ... Griffioen, A. W. (2008). Angiostatic activity of the antitumor cytokine interleukin-21. Blood, 112(13), 4940-4947. https://doi.org/10.1182/blood-2007-09-113878

Angiostatic activity of the antitumor cytokine interleukin-21. / Castermans, Karolien; Tabruyn, Sebastien P.; Zeng, Rong; Van Beijnum, Judy R.; Eppolito, Cheryl; Leonard, Warren J.; Shrikant, Protul A.; Griffioen, Arjan W.

In: Blood, Vol. 112, No. 13, 15.12.2008, p. 4940-4947.

Research output: Contribution to journalArticle

Castermans, K, Tabruyn, SP, Zeng, R, Van Beijnum, JR, Eppolito, C, Leonard, WJ, Shrikant, PA & Griffioen, AW 2008, 'Angiostatic activity of the antitumor cytokine interleukin-21', Blood, vol. 112, no. 13, pp. 4940-4947. https://doi.org/10.1182/blood-2007-09-113878
Castermans K, Tabruyn SP, Zeng R, Van Beijnum JR, Eppolito C, Leonard WJ et al. Angiostatic activity of the antitumor cytokine interleukin-21. Blood. 2008 Dec 15;112(13):4940-4947. https://doi.org/10.1182/blood-2007-09-113878
Castermans, Karolien ; Tabruyn, Sebastien P. ; Zeng, Rong ; Van Beijnum, Judy R. ; Eppolito, Cheryl ; Leonard, Warren J. ; Shrikant, Protul A. ; Griffioen, Arjan W. / Angiostatic activity of the antitumor cytokine interleukin-21. In: Blood. 2008 ; Vol. 112, No. 13. pp. 4940-4947.
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