Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-α and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor

Abstract

Abstract. 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-α, LIF, IL-1ß, IL-6, IL-8, or IFN-ß 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-α or not. The half-life of CXCL-8 mRNA was 36.5 min by TNF-α 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-κB 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.

CXC‐chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer

“…In PaCa, there are a few reports that suggest possible autocrine effects of CXCL8 in proliferation using Capan-1 and SUIT-2 pancreatic cancer cell lines. [34][35][36][37] Conversely, our previous study demonstrated that the majority of PaCa cell lines examined did not express CXCR2. 24 Moreover, in this study, we showed that ELR 1 -CXC-chemokines did not affect proliferation of commonly used PaCa cell lines including BxPC-3 and MIA PaCa-2.…”

Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance

“…Among them, only LIF-mediated STAT3 signaling has been defined in detail. Recently, dysregulation of LIF and/or the LIF receptor (LIFR) has been reported in several human malignancies, including glioblastoma (21), thyroid cancer (22), rhabdomyosarcoma (23), pancreatic carcinoma (24,25), and breast cancer (26). However, the precise role of LIF in tumorigenesis remains largely unexplored.…”

GPCRs and cancer

“…The first described angiogenic chemokine, CXCL8/IL-8, which binds to CXCR1 and CXCR2 [78] , is secreted by a variety of normal and tumor cells exposed to pro-inflammatory cytokines like IL-1 and TNF-α [79] . CXCR2 was associated to multiple signaling pathways involved in tumorigenesis, angiogenesis, proliferation and metastasis in several malignancies, including melanoma [80] , lung [81] , pancreatic [79,82] , gastric [83] , and ovarian [57] tumors. For instance, the overexpression of CXCR2 induced an aggressive phenotype of melanoma cells consisting with an enhanced proliferation, migration and tumor growth in mice [84] .…”