期刊
CANCER RESEARCH
卷 66, 期 1, 页码 57-61出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-3445
关键词
-
类别
资金
- NCI NIH HHS [P01CA26731, R01CA108854, R01CA67529] Funding Source: Medline
- NCRR NIH HHS [T32RR07036] Funding Source: Medline
- NIAID NIH HHS [R01 AI50952] Funding Source: Medline
- NIDDK NIH HHS [R01 DK52413] Funding Source: Medline
- NIEHS NIH HHS [P30ES02109] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA108854, P01CA026731, R01CA067529] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [T32RR007036] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI050952] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK052413] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES002109] Funding Source: NIH RePORTER
Cancers of breast and bowel are increasingly frequent in humans. Chronic inflammation is known to he a risk factor for these malignancies, yet cellular and molecular mechanisms linking inflammation and carcinogenesis remain poorly understood. Here, we apply a widely used T-cell transfer paradigm, involving adoptive transfer of proinflammatory CD4(+)CD45RB(hi) (T-E) cells to induce inflammatory bowel disease (IBD) in mice, to investigate roles of inflammation on carcinogenesis in the Apc(Min/+) mouse model of intestinal polyposis. We find that transfer of T-E cells significantly increases adenoma multiplicity and features of malignancy in recipient Apc(Min/+) mice. Surprisingly, we find that female Apc(Min/+) recipients of T-E cells also rapidly develop mammary tumors. Both intestinal polyposis and mammary adenocarcinoma are abolished by cotransfer of anti-inflaminatory CD4(+)CD45RB(lo) regulatory lymphocytes or by neutralization of key proinflammatory cytokine tumor necrosis factor-alpha. Lastly, down-regulation of cyclooxygenase-2 and c-Myc expression is observed coincident with tumor regression. These findings define a novel mouse model of inflammation-driven mammary carcinoma and suggest that epithelial carcinogenesis can be mitigated by anti-inflammatory cells and cytokines known to regulate IBD in humans and mice.
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