LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation

Abstract

Tumor-associated macrophage (TAM)-related chronic inflammation and interleukin-6 (IL-6) contribute to the progression of nasopharyngeal carcinoma (NPC). In this study, we characterized TAMs and IL-6 expression in 212 biopsied NPC and 119 non-tumor nasopharyngeal epithelium (NPE) tissues by tissue array. In comparison with that in the NPE tissues, more TAM infiltrates and a higher density of IL-6 expression were detected in NPC tissues, which were associated with the poor survival of NPC patients. In contrast, little or no LPLUNC1, a regulator of inflammation, expression was detected in NPC tissues, and the levels of LPLUNC1 expression in the NPC were associated negatively with the numbers of TAMs and the levels of IL-6 expression, but positively with the survival of NPC patients. Induction of LPLUNC1 overexpression in NPC cells mitigated lipopolysaccharide (LPS)-induced IL-6, IL-8, tumor necrosis factor-α and IL-1β expression or treatment of THP-1 macrophages with LPLUNC1 inhibited spontaneous and LPS-induced IL-6 expression in vitro. IL-6-promoted NPC cell proliferation in a dose- and time-dependent manner, accompanied by increasing cyclin D1 and Bcl-2 expression and the Stat3 activation, but inhibiting Bax and p21 expression. Induction of LPLUNC1 overexpression inhibited NPC cell proliferation, induced NPC cell arrest, promoted NPC cell apoptosis even after IL-6 stimulation and inhibited the growth of implanted NPC tumors in vivo, which were associated with decreasing cyclin D1 and Bcl-2 expression and the Janus kinase 2 (JAK2)/Stat3 activation, but enhancing Bax and p21 expression. These results suggest that LPLUNC1 can inhibit inflammation and NPC growth by downregulating the Stat3 pathway.

Serum C-Reactive Protein Predicts Poor Prognosis in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

“…A member of the bactericidal permeability-increasing protein and lipid-binding protein family, lplunc1 can be secreted by goblet cells and minor mucosal glands of the upper respiratory tract and oral cavity 13 . The protein inhibits lipopolysaccharide-induced interleukin 6 expression in npc cells and thus inhibits npc cell proliferation, induces npc cell arrest, and promotes npc cell apoptosis 12,13 . The correlation between elevated serum crp and a poor prognosis might reflect the prognostic value of tumour-produced interleukin 6, an inducer of crp production in the liver 14 .…”

Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network

“…Western blotting was performed as described previously [30][31][32]. Cell lysates were separated by electrophoresis on 10 % sodium dodecyl sulfate (SDS) polyacrylamide gels, and the separated proteins were transferred to a polyvinylidene fluoride (PVDF) membrane (Millipore, Billerica, MA).…”

Pre-treatment serum inflammatory cytokines as survival predictors of patients with nasopharyngeal carcinoma receiving chemoradiotherapy

“…progression and tumor metastasis. Liao et al (27) used NPC cell lines to detect that IL-6 promoted NPC cell proliferation in a dose-and time-dependent manner, and this was accompanied by increasing cyclin D1 and Bcl-2 expression, STAT-3 activation, and inhibition of Bax and p21 expression. Liu et al (28) observed that in certain macrophages of the tumor stroma of NPC tissue, IL-6-and TNF-α-dependent expression of tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase led to suppressed proliferation of T cells and impaired cytotoxic activity of CD8(+) T cells, thus facilitating immune escape.…”