| First Author | Moore RJ | Year | 1999 |
| Journal | Nat Med | Volume | 5 |
| Issue | 7 | Pages | 828-31 |
| PubMed ID | 10395330 | Mgi Jnum | J:56068 |
| Mgi Id | MGI:1339934 | Doi | 10.1038/10552 |
| Citation | Moore RJ, et al. (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5(7):828-831 |
| abstractText | Given the associations between chronic inflammation and epithelial cancer(1,2) , we studied susceptibility to skin carcinogenesis(3,4) in mice deficient for the pro- inflammatory cytokine TNF-alpha (refs. 5,6). TNF-alpha(-/- ) mice were resistant to development of benign and malignant skin tumors, whether induced by initiation with DMBA and promotion with TPA or by repeated dosing with DMBA. TNF-alpha(-/-) mice developed 5-10% the number of tumors developed by wild-type mice during initiation/ promotion and 25% of those in wild-type mice after repeated carcinogen treatment. TNF-alpha could influence tumor and stromal cells during tumor development. The early stages of TPA promotion are characterized by keratinocyte hyperproliferation and inflammation. These were diminished in TNF-alpha(-/-) mice. TNF-alpha was extensively induced in the epidermis, but not the dermis, in TPA-treated wild-type skin, indicating that dermal inflammation is controlled by keratinocyte TNF-a production. Deletion of a TNF-alpha inducible chemokine also conferred some resistance to skin tumor development. TNF-alpha has little influence on later stages of carcinogenesis, as tumors in wild-type and TNF-alpha(-/-) mice had similar rates of malignant progression. These data provide evidence that a pro-inflammatory cytokine is required for de novo carcinogenesis and that TNF-alpha is important to the early stages of tumor promotion. Strategies that neutralize TNF-alpha production may be useful in cancer treatment and prevention. |
