| First Author | Bauer O | Year | 2014 |
| Journal | Cancer Prev Res (Phila) | Volume | 7 |
| Issue | 9 | Pages | 913-26 |
| PubMed ID | 24961879 | Mgi Jnum | J:290002 |
| Mgi Id | MGI:6441094 | Doi | 10.1158/1940-6207.CAPR-14-0098-T |
| Citation | Bauer O, et al. (2014) Carcinogen-induced skin tumor development requires leukocytic expression of the transcription factor Runx3. Cancer Prev Res (Phila) 7(9):913-26 |
| abstractText | Carcinogen-induced skin tumorigenesis depends heavily on proinflammatory tumor-promoting processes. Here, we show that leukocytic Runx3 expression is central to the two-stage DMBA/TPA-induced skin tumorigenesis. Runx3-null mice were highly resistant to this process and concomitant ablation of Runx3 in dendritic and T cells fully recapitulated this resistance. Mechanistically, this resistance was associated with a shift in the skin cytokine milieu toward a tumor nonpermissive microenvironment. Specifically, leukocytic Runx3 loss substantially increased the antitumorigenic cytokine thymic stromal lymphopoietin (TSLP) and profoundly decreased two protumorigenic cytokines, interleukin-17a and osteopontin. Therefore, inflammation-mediated tumor promotion requires leukocytic Runx3 expression, as its loss creates a unique cytokine composition that polarizes the tumor microenvironment to a potent antitumorigenic state. |
