Abstract
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.
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Acknowledgments
This work is supported by funding from the National Science Foundation of China (81171930, 30871282, 30871365, 30971147, 81071644, 81172189, 81101509), the 111 project (111-2-12), the Program for New Century Excellent Talents in University (NCET-08-0562) and the Hunan Province Natural Sciences Foundation of China (10JJ7003).
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The authors declare no conflict of interest.
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Q. Liao and X. Guo contributed equally to this work.
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Liao, Q., Guo, X., Li, X. et al. Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response. J Cancer Res Clin Oncol 138, 57–64 (2012). https://doi.org/10.1007/s00432-011-1066-1
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DOI: https://doi.org/10.1007/s00432-011-1066-1