Pathogenic role of Epstein–Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma

Yoshizaki, Tomokazu; Kondo, Satoru; Wakisaka, Naohiro; Murono, Shigeyuki; Endo, Kazuhira; Sugimoto, Hisashi; Nakanishi, Sayaka; Tsuji, Akira; Ito, Makoto

doi:10.1016/j.canlet.2013.05.018

Cited by 125 publications

(116 citation statements)

References 86 publications

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“…1 One important consequence of EBV infection is malignant transformation of epithelial cells, promoted by EBV-encoded protein and microRNAs. [26][27][28][29] Another is EBV-induced inflammatory cytokines in the tumor microenvironment, resulting in angiogenesis and metastasis. 8 As a key component of innate immunity, LF has vital roles in host defense against infection and excessive inflammation.…”

Section: Lf Expression Levels Correlated Inversely With Mcp-1 and Il-mentioning

confidence: 99%

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Zheng

Qin²,

Ye³

et al. 2014

Laboratory Investigation

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Epstein-Barr virus (EBV) infection contributes to tumorigenesis of various human malignancies including nasopharyngeal carcinoma (NPC). EBV triggers innate immune and inflammatory responses partly through Toll-like receptor (TLR) signaling. Lactoferrin (LF), with its anti-inflammatory properties, is an important component of the innate immune system. We previously reported that LF protects human B lymphocytes from EBV infection by its ability to bind to the EBV receptor CD21, but whether LF can suppress EBV-induced inflammation is unclear. Here, we report that LF reduced synthesis of IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by EBV in macrophages via its suppression of NF-kB activity. LF interacted with TLR2 and interfered with EBV-triggered TLR2-NF-kB activation. LF inhibited the ability of TLR9 to recognize dsDNA by binding to its co-receptor CD14, which blocked the interaction between CD14 and TLR9. EBV-induced inflammation was thus aggravated in the presence of CD14. In addition, LF expression levels were significantly downregulated in NPC specimens, and correlated inversely with IL-8 and MCP-1 expression. These findings suggest that LF may suppress the EBV-induced inflammatory response through interfering with the activation of TLR2 and TLR9.

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Section: Lf Expression Levels Correlated Inversely With Mcp-1 and Il-mentioning

confidence: 99%

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Zheng

Qin²,

Ye³

et al. 2014

Laboratory Investigation

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“…Infection with the Epstein-Barr virus (EBV) is considered a key cause of NPC (1) , but the ubiquity of EBV suggests that other cofactors, such as diet, may have a role in NPC aetiology and may contribute to the remarkable geographic variation (4,5) . However, the role of diet has scarcely been investigated.…”

mentioning

confidence: 99%

Folate, vitamin B₆, vitamin B₁₂ and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case–control study

et al. 2015

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Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B 6 , vitamin B 12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B 6 , vitamin B 12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B 6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 0·66 (95 % CI 0·48, 0·91), 0·52 (95 % CI 0·37, 0·74) and 0·34 (95 % CI 0·23, 0·50) (P trend < 0·001) for folate and 0·72 (95 % CI 0·52, 1·00), 0·55 (95 % CI 0·39, 0·78) and 0·44 (95 % CI 0·30, 0·63) (P trend < 0·001) for vitamin B 6 . No significant association with NPC risk was observed for dietary vitamin B 12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P interaction = 0·014). This study suggests that dietary folate and vitamin B 6 may be protective for NPC in a high-risk population.

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“…In view of continuous presence of Epstein-Barr Virus (EBV) in C666-1 (Cheung et al, 1999;, the EBV oncogenes probably participate in the regulation mechanisms of Pokemon, even promote Pokemon protein expression and in coordination with elevating tumorigenicity of EBV products, which play an pathogenic role in the development of NPC (Yip et al, 2010;Yoshizaki et al, 2013). According to WHO classification system standard (2005), the pathological type of C666-1 is UCNT.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Pokemon Proto-oncogene in Nasopharyngeal Carcinoma Cell Lines and Tissues

Jiao

Liu²,

Tang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy.

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Pathogenic role of Epstein–Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma

Cited by 125 publications

References 86 publications

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Folate, vitamin B₆, vitamin B₁₂ and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case–control study

Expression of the Pokemon Proto-oncogene in Nasopharyngeal Carcinoma Cell Lines and Tissues

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Pathogenic role of Epstein–Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma

Cited by 125 publications

References 86 publications

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case–control study

Expression of the Pokemon Proto-oncogene in Nasopharyngeal Carcinoma Cell Lines and Tissues

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Folate, vitamin B₆, vitamin B₁₂ and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case–control study