Abstract 402: The role of IL-6 in communication of pancreatic carcinoma cells with fibroblasts

Abstract

Abstract <INTRODUCTION> Pancreatic cancer shows high mortality rates in gastroenterogical neoplasms, and there are difficulties in early diagnosis and aggressive progression. IL-6 has pleiotropic function and are produced by various immunnocompetent cells, as well as cancer cells. Some studies have been demonstrated IL-6 play an important role in evading host immune surveillance in tumor microenvironment, but interactions of fibroblasts has not been fully understood. Therefore, the aim of this study is to reveal role of fibroblasts in pancreatic tumor microenvironment. Especially, we evaluate induction and biologicial function of IL-6 in pancreatic carcinoma cells after the stimulation with various cytokines and fibroblast associated factors. <METHODS and RESULTS> Firstly, we examined IL-6 and its receptors expression by RT-PCR and Northern blotting. All 7 tested cell lines expressed gp130 and IL-6R alpha mRNA, 2 cell lines (Hs7667 and Capan1) expressed IL-6 mRNA in serum free condition. To clarify the effect of proinflammatory cytokines on IL-6 expression in Hs766T cells, cells were stimulated with or without cytokines. Northern blotting revealed TNFα and IL-1β upregulated IL-6 mRNA, but not IL-6, IL-8 and LIF. IL-6 did not affect cell proliferation by WTS assay in 7 pancreatic carcinoma cells. In contrast, IL-6 promoted cell motility significantly by gold particles phagocytosis assay (P<0.05) and cell invasion significantly by matrigel insert chamber assay (P<0.05). IL-6 induces phosphorylation of STAT3 in Hs-766T cells, but not AKT. To identify IL-6 expression by interaction between pancreatic carcinoma cells and fibroblasts, we used two established fibroblastic cell lines (MRC-9 and WI-38) isolated from human embryonal lung tissues. Serum free conditioned medium (CM) were collected after incubation for indicated periods. Hs766T originated CM (Hs766T-CM) induced IL-6 and IL-8 mRNA in MRC-9 and WI-38 cells. MRC-9 CM and WI-38-CM did not affect in Hs-766T cells. Co-culture between Hs-766T and MRC-9 cells induced IL-8 mRNA dratically. IL-6 promotes miR-146a and miR155 expression in Hs-766T cells. <CONCLUSIONS> Communication of pancreatic carcinoma cells with fibroblasts affect IL-6 expression and it could contribute to pancreatic cancer progression. Regulation of IL-6 expression in tumor microenvironment would be important for pancreatic cancer therapy. 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 402. doi:10.1158/1538-7445.AM2011-402