Abstract 4111: Induction of CXCL8 by TNFalpha and LIF (Leukemia Inhibitory Factor) in pancreatic carcinoma cells: Impact of CXCL8 as an autocrine growth factor

Abstract

Abstract <INTRODUCTION> Pancreatic carcinoma is one of the most lethal in the gastroenterogical malignant tumors. Chronic inflammation cause to cancer development and progression. CXCL8 is a CXC chemokine, which play an important role in neutrophil chemotaxis and activation. We previously reported that CXCL8 was produced by a variety of human carcinoma cells and tissues and that CXCL8 also promoted proliferation in pancreatic carcinoma cells. In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL8 induction in pancreatic carcinoma cells. <METHODS and RESULTS> Eight examined pancreas carcinoma cell lines expressed CXCL8, CXCR1 CXCR2 and TNFRII mRNA constitutively in RPMI1640 medium without FBS. TNFalpha, LIF, IL1beta, IL6, CXCL8, or IFNbeta enhanced the expression of CXCL8 mRNA, but IL10 did not in Hs-700T cells. Especially, TNFalpha was a robust inducer. Actinomycin D suppressed and cycloheximide augmented CXCL8 mRNA which was induced by TNFalpha, LIF or not. The half-life of CXCL8 mRNA was 36.5 min by TNFalpha and 35.2 min without stimulation. That indicated the stability of CXCL8 mRNA was not affected by the stimulation of TNFalpha. Nextly, we examined the effect of CXCL8 on cell growth in Hs700T cells. Addition of recombinant TNFalpha or CXCL8 did not promoted cell growth of Hs700T. High amount of CXCL8 induced by TNFalpha or CXCL8 did not reponse to cell growth. On the other hand, LIF promoted cell growth after activation of STAT3 phosphrylation in Hs-700T cells by IP-Western blotting. The cell growth mechanism by LIF would depend on STAT3 activation. Anti-CXCL8 IgG significantly suppressed cell growth Hs-700T cells. Optimized concentration of CXCL8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL8 mRNA highly without stimulation. Curcumin (Diferuloylmethane), NF-kappaB inhibitor, suppressed cell proliferation in Hs-700T cells. <CONCLUSION> These results suggest that CXCL8 play a pivotal role in development and progression of pancreatic cancer, and its expression is regulated by inflammatory cytokines. High concentration of CXCL8 produced by cancer cells could affect neigboring cells in pancreatic tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4111.