| First Author | Cao Y | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 4 | Pages | 1235-43 |
| PubMed ID | 21159661 | Mgi Jnum | J:169321 |
| Mgi Id | MGI:4940437 | Doi | 10.1158/0008-5472.CAN-10-2217 |
| Citation | Cao Y, et al. (2011) B7-h1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin. Cancer Res 71(4):1235-43 |
| abstractText | B7-H1 (CD274) is a T-cell coinhibitory molecule that is also often induced on human carcinoma cells, where its expression has been implicated in immune escape. Under inflammatory conditions, B7-H1 is also inducible in normal epithelial cells but little is known about its involvement in conversion of normal cells to tumor cells. Here, we show that skin-specific expression of B7-H1 accelerates inflammatory carcinogenesis in a methylcholantrene (MCA)-induced model of squamous cell carcinoma (SCC). Inflammatory responses induced by MCA or phorbol ester TPA were clearly inhibited in B7-H1 transgenic mice (B7-H1tg mice). Antibody-mediated blockade of either B7-H1 or the related molecule PD-1 revealed that their ability to limit inflammation relied on ligand interactions made by B7-H1 or PD-1. Skin keratinocytes derived from B7-H1tg mice exhibited constitutive reduction of E-cadherin, and SCC induced in B7-H1tg mice also showed loss of E-cadherin along with elevated expression of the transcription factors Slug and Twist that drive epithelial-mesenchymal transition (EMT). Our results indicate that upregulation of B7-H1 in skin epithelial cells promotes EMT and accelerates carcinogenesis, revealing insights into the significance of B7-H1 overexpression on solid tumor cells and hinting at a close relationship between EMT and immune escape signaling pathways in cancer. Cancer Res; 71(4); 1235-43. (c)2010 AACR. |
