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Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1\u03b2 KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1\u03b2 KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1\u03b1 KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1\u03b2 KO mice. These effects of host-derived IL-1\u03b1 and IL-1\u03b2 were not restricted to the melanoma model, but were also observed in DA\/3 mammary and prostate cancer cell models. In addition to the\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0437939100","type":"journal-article","created":{"date-parts":[[2003,3,4]],"date-time":"2003-03-04T13:36:00Z","timestamp":1046784960000},"page":"2645-2650","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":878,"title":["IL-1 is required for tumor invasiveness and angiogenesis"],"prefix":"10.1073","volume":"100","author":[{"given":"Elena","family":"Voronov","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology, and Pathology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; Institute of Medical Science, University of Tokyo, Minato-Ku 108-8639, Japan; and University of Colorado Health Sciences Center, 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