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Blood, 15 December 2008, Vol. 112, No. 13, pp. 4940-4947. Prepublished online as a Blood First Edition Paper on May 30, 2008; DOI 10.1182/blood-2007-09-113878. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-09-113878v1 112/13/4940    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Castermans, K. Articles by Griffioen, A. W. Search for Related Content PubMed PubMed Citation Articles by Castermans, K. Articles by Griffioen, A. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Angiostatic activity of the antitumor cytokine interleukin-21 Karolien Castermans1, Sebastien P. Tabruyn1, Rong Zeng2, Judy R. van Beijnum1, Cheryl Eppolito3, Warren J. Leonard2, Protul A. Shrikant3, and Arjan W. Griffioen1 1 Angiogenesis Laboratory, School for Oncology and Developmental Biology, Departments of Pathology and Internal Medicine, Maastricht University and University Hospital, Maastricht, The Netherlands; 2 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD; and 3 Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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