Abstract 4268: Interleukin-27 inhibits angiogenesis in non-small cell lung cancer

Abstract

Abstract Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Angiogenesis is a critical process during carcinogenesis. We investigated the role of IL-27 in tumor angiogenesis in lung cancer. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and human non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot after IL-27 exposure demonstrated activation of both pathways in these cell lines. Protein production of an important pro-angiogenic factor, vascular endothelial growth factor (VEGF), was measured by ELISA and Western analysis. After exposure to IL-27, there was a 60-80% decrease in VEGF protein expression of VEGF by ELISA (confirmed by Western analysis in the NSCLC lines but not in the HBECs or their genetically modified derivatives). The IL-27 down regulation of VEGF was not increased by the addition of a STAT3 inhibitor. In summary, IL-27 inhibits VEGF production in NSCLC through a mechanism independent of STAT3, suggesting that STAT1 may play a dominant role in IL-27 mediated angiogenesis suppression. 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 4268. doi:10.1158/1538-7445.AM2011-4268