期刊
CANCER RESEARCH
卷 76, 期 24, 页码 7106-7117出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-1456
关键词
-
类别
资金
- NIH [P01CA186866, R01CA188419, R01AI070603, P30CA138313, TL1 TR001451, UL1 TR001450, P30 CA138313]
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGF beta, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGF beta in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGF beta bioactivity and promoted malignant transformation in immunodeficient mice. In breast carcinoma-bearing mice that were immunocompetent, GARP overexpression promoted Foxp(3+) Treg activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a GARP-specific mAb limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGF beta axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. (C)2016 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据