Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response.

PURPOSE: We investigated the local contribution of nasopharyngeal epithelial cancer cells to the inflammatory process.
MATERIALS AND METHODS: THP-1 monocytes were treated with phorbol 12-myristate 13-acetate to induce the production of differentiated macrophages (D-THP-1), which were subsequently activated by lipopolysaccharide (LPS) (10 ng/ml). The production of pro-inflammatory cytokines in D-THP-1 cells was detected by ELISA and qRT-PCR. The effects of conditioned media harvested from LPS-treated D-THP-1 cells were investigated with regard to cell proliferation (MTT), production of pro-inflammatory cytokines (ELISA) and activation of NF-κB and STAT3 (western blot) in the nasopharyngeal epithelial cancer cell line 5-8F.
RESULTS: LPS induced the production of the pro-inflammatory cytokines TNF-α (875.1 ± 68.31 pg/ml), IL-6 (42.2 ± 5.32 pg/ml), IL-1β (9.6 ± 1.34 pg/ml) and IL-8 (19.3 ± 3.47 pg/ml) in D-THP-1 cells significantly (P < 0.001) with similar results detected at the mRNA level. Exposure of 5-8F cells to conditioned medium from LPS-treated D-THP-1 cells significantly induced production of TNF-α (632.3 ± 71.32 pg/ml), IL-6 (51.3 ± 3.57 pg/ml), IL-1β (7.3 ± 1.31 pg/ml) and IL-8 (20.1 ± 2.36 pg/ml) (P < 0.01) and triggered significant activation of NF-κB and STAT3, which correlated with a concomitant degradation of IκBα and an increase in JAK2 phosphorylation (P < 0.05). Moreover, the LPS-treated D-THP-1 conditioned media promoted the proliferation of 5-8F cells (P < 0.05).
CONCLUSIONS: Nasopharyngeal epithelial cancer cells may play a significant role in maintaining and amplifying the inflammation process via activation of NF-κB and STAT3 pathway and through the local production of pro-inflammatory cytokines, which recruit and activate additional immune cells in the nasopharyngeal path and promote tumour progression.