文章基本信息

标题：α-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis
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作者：Yoshihiro Hayakawa ; Stefania Rovero ; Guido Forni 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：16
页码：9464-9469
DOI：10.1073/pnas.1630663100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recent studies have revealed significant efficacy of the marine sponge glycolipid, -galactosylceramide (-GalCer), in treatment of experimental metastatic cancers, infections, and autoimmune diseases. However, the capacity of -GalCer to prevent tumor development had never, to our knowledge, been evaluated in mouse models of chemical- and oncogene-dependent carcinogenesis. In this study, we demonstrate that long-term administration of soluble -GalCer, spanning the time of tumor initiation, inhibits primary tumor formation in three different models: methylcholanthrene-induced sarcomas, mammary carcinomas in Her-2/neu transgenic mice, and spontaneous sarcomas in p53-/- mice. Weekly treatment of mice with -GalCer maintained lymphoid tissue natural killer cell and T cell activation and elevated serum IFN-{gamma} and IL-4 concentrations. Consistent with the antimetastatic activity of -GalCer, prevention of methylcholanthrene-induced sarcoma was IFN-{gamma}and tumor necrosis factor-related apoptosis-inducing ligand dependent, but not perforin-dependent. Taken together, our results demonstrate that NK1.1+{beta}TCR+ cell-based immune therapy can inhibit primary tumorigenesis.