Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor.
Pancreatic carcinoma is one of the most lethal of the gastrointestinal malignant tumors. Chronic inflammation leads to cancer development and progression. Interleukin-8 (CXCL-8) is a CXC chemokine, which plays an important role in neutrophil chemotaxis and activation. We previously reported that CXCL-8 was produced by a variety of human carcinoma cells and tissues, and that CXCL-8 promoted proliferation in pancreatic carcinoma cells (SUIT-2). In the present study, we analyzed whether various cytokines affect cell proliferation by CXCL-8 expression in pancreas carcinoma cells. All examined pancreatic carcinoma cells expressed CXCL-8 and TNFRII mRNA constitutively in RPMI-1640 medium without FBS. TNF-alpha, LIF, IL-1beta, IL-6, IL-8, or IFN-beta enhanced the expression of CXCL-8 mRNA, but IL-10 did not in Hs-700T cells. Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-alpha or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-alpha and 35.2 min by no stimulation. In our previous study, LIF promoted cell growth in Hs-700T cells. LIF induced CXCL-8 mRNA in a dose- and time-dependent manner. Addition of recombinant CXCL-8 did not induce cell growth of Hs-700T. Anti-CXCL-8 IgG significantly suppressed cell growth. CXCL-8 would act as an autocrine growth factor in Hs-700T cells, which expressed CXCL-8 mRNA highly without stimulation. Curcumin (diferuloylmethane), NF-kappaB inhibitor, suppressed cell proliferation in Hs-700T cells. These results suggest that CXCL-8 plays a pivotal role in progression of pancreatic cancer, and its expression is influenced by inflammatory cytokines in pancreatic tumor microenvironment.
Kamohara
Hidenobu
H
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. kamo.kamo@tkg.bbiq.jp
Takahashi
Masashi
M
Ishiko
Takatoshi
T
Ogawa
Michio
M
Baba
Hideo
H
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide