Abstract 5542: Chronic TNF-α treatment augments malignant properties of HPV-immortalized oral keratinocytes

Abstract

While acute inflammation is a part of the defense response, there have been emerging lines of evidence that suggest a strong link between chronic inflammation and cancer. Human papillomaviruses (HPV) infection is one of key factors in cervical cancer development, and possible link between HPV and oral carcinogenesis have been proposed. However, mechanisms by which HPV and chronic inflammation contribute to oral carcinogenesis have not been fully understood. The objective of this study was to determine the effect of chronic inflammation on malignant progression of HPV-associated oral carcinogenesis. We treated HPV-immortalized oral keratinocytes (HOK-16B) with a major pro-inflammatory cytokine, TNF-α for 4 months and examined the effect of chronic TNF-α treatment on malignant behavior of HOK-16B. Chronic treatment of TNF-α resulted in reduction in differentiation potential, and induction in proliferation potential and in migration ability of the HPV-immortalized oral keratinocytes. cDNA microarray analysis revealed that a subset of genes was significantly downregulated in long-term TNF-α treated cells, and the genes that were involved in differentiation, tumor suppression, and cell-cell junction functions supported the three increased malignant phenotypes, respectively. Our results indicate that chronic inflammation promotes malignant behavior of HPV-immortalized oral keratinocytes, suggesting that chronic inflammation is an important co-carcinogenic factor for HPV-associated oral carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5542. doi:10.1158/1538-7445.AM2011-5542