| First Author | Lee CH | Year | 2015 |
| Journal | J Cell Physiol | Volume | 230 |
| Issue | 4 | Pages | 875-84 |
| PubMed ID | 25204733 | Mgi Jnum | J:317000 |
| Mgi Id | MGI:6843879 | Doi | 10.1002/jcp.24816 |
| Citation | Lee CH, et al. (2015) IL-1beta promotes malignant transformation and tumor aggressiveness in oral cancer. J Cell Physiol 230(4):875-84 |
| abstractText | Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1beta) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1beta expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1beta was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1beta secretion in an inflammasome-dependent manner. IL-1beta treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-alpha following IL-1beta stimulation. The conditioned medium of IL-1beta-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1beta increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1beta can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. |
