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Erschienen in: Journal of Cancer Research and Clinical Oncology 1/2012

01.01.2012 | Original Paper

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

verfasst von: Qianjin Liao, Xiaofang Guo, Xiaoling Li, Xiayu Li, Pan Chen, Fang Liang, Hailin Tang, Min Deng, Minghua Wu, Jian Ma, Wei Xiong, Guiyuan Li

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2012

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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.
Literatur
Zurück zum Zitat Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15(2):103–113. doi:10.1016/j.ccr.2009.01.001 PubMedCrossRef Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15(2):103–113. doi:10.​1016/​j.​ccr.​2009.​01.​001 PubMedCrossRef
Zurück zum Zitat Gullo C, Low WK, Teoh G (2008) Association of Epstein-Barr virus with nasopharyngeal carcinoma and current status of development of cancer-derived cell lines. Ann Acad Med Singapore 37(9):769–777PubMed Gullo C, Low WK, Teoh G (2008) Association of Epstein-Barr virus with nasopharyngeal carcinoma and current status of development of cancer-derived cell lines. Ann Acad Med Singapore 37(9):769–777PubMed
Zurück zum Zitat Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, Yagita H, Takaoka A, Tahara H (2011) Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci USA 108(30):12425–12430. doi:10.1073/pnas.1106645108 PubMedCrossRef Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, Yagita H, Takaoka A, Tahara H (2011) Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci USA 108(30):12425–12430. doi:10.​1073/​pnas.​1106645108 PubMedCrossRef
Zurück zum Zitat Pina Y, Boutrid H, Murray TG, Jager MJ, Cebulla CM, Schefler A, Ly LV, Alegret A, Celdran M, Feuer W, Jockovich ME (2010) Impact of tumor-associated macrophages in LH(BETA)T(AG) mice on retinal tumor progression: relation to macrophage subtype. Invest Ophthalmol Vis Sci 51(5):2671–2677. doi:10.1167/iovs.09-4255 PubMedCrossRef Pina Y, Boutrid H, Murray TG, Jager MJ, Cebulla CM, Schefler A, Ly LV, Alegret A, Celdran M, Feuer W, Jockovich ME (2010) Impact of tumor-associated macrophages in LH(BETA)T(AG) mice on retinal tumor progression: relation to macrophage subtype. Invest Ophthalmol Vis Sci 51(5):2671–2677. doi:10.​1167/​iovs.​09-4255 PubMedCrossRef
Zurück zum Zitat Shieh YS, Hung YJ, Hsieh CB, Chen JS, Chou KC, Liu SY (2009) Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands. Ann Surg Oncol 16(3):751–760. doi:10.1245/s10434-008-0259-6 PubMedCrossRef Shieh YS, Hung YJ, Hsieh CB, Chen JS, Chou KC, Liu SY (2009) Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands. Ann Surg Oncol 16(3):751–760. doi:10.​1245/​s10434-008-0259-6 PubMedCrossRef
Zurück zum Zitat Xiong W, Zeng ZY, Xia JH, Xia K, Shen SR, Li XL, Hu DX, Tan C, Xiang JJ, Zhou J, Deng H, Fan SQ, Li WF, Wang R, Zhou M, Zhu SG, Lu HB, Qian J, Zhang BC, Wang JR, Ma J, Xiao BY, Huang H, Zhang QH, Zhou YH, Luo XM, Zhou HD, Yang YX, Dai HP, Feng GY, Pan Q, Wu LQ, He L, Li GY (2004) A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res 64(6):1972–1974PubMedCrossRef Xiong W, Zeng ZY, Xia JH, Xia K, Shen SR, Li XL, Hu DX, Tan C, Xiang JJ, Zhou J, Deng H, Fan SQ, Li WF, Wang R, Zhou M, Zhu SG, Lu HB, Qian J, Zhang BC, Wang JR, Ma J, Xiao BY, Huang H, Zhang QH, Zhou YH, Luo XM, Zhou HD, Yang YX, Dai HP, Feng GY, Pan Q, Wu LQ, He L, Li GY (2004) A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res 64(6):1972–1974PubMedCrossRef
Zurück zum Zitat Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR (2007a) Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev 21(11):1396–1408. doi:10.1101/gad.1553707 PubMedCrossRef Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR (2007a) Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev 21(11):1396–1408. doi:10.​1101/​gad.​1553707 PubMedCrossRef
Zurück zum Zitat Yang Y, Zhou H, Li W, Zhou M, Zeng Z, Xiong W, Wu M, Huang H, Zhou Y, Peng C, Huang C, Li X, Li G (2007b) Lipopolysaccharide (LPS) regulates TLR4 signal transduction in nasopharynx epithelial cell line 5–8F via NFkappaB and MAPKs signaling pathways. Mol Immunol 44(5):984–992. doi:10.1016/j.molimm.2006.03.013 PubMedCrossRef Yang Y, Zhou H, Li W, Zhou M, Zeng Z, Xiong W, Wu M, Huang H, Zhou Y, Peng C, Huang C, Li X, Li G (2007b) Lipopolysaccharide (LPS) regulates TLR4 signal transduction in nasopharynx epithelial cell line 5–8F via NFkappaB and MAPKs signaling pathways. Mol Immunol 44(5):984–992. doi:10.​1016/​j.​molimm.​2006.​03.​013 PubMedCrossRef
Metadaten
Titel
Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response
verfasst von
Qianjin Liao
Xiaofang Guo
Xiaoling Li
Xiayu Li
Pan Chen
Fang Liang
Hailin Tang
Min Deng
Minghua Wu
Jian Ma
Wei Xiong
Guiyuan Li
Publikationsdatum
01.01.2012
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1066-1

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