国际口腔医学杂志

国际口腔医学杂志 ›› 2017, Vol. 44 ›› Issue (5): 596-601.doi: 10.7518/gjkq.2017.05.021

• 综述 • 上一篇    下一篇

Toll样受体9与头颈部鳞状细胞癌关系的研究进展

张煦, 许恩馨, 阮敏   

  1. 上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科,上海市口腔医学重点实验室/上海市口腔医学研究所,国家口腔疾病临床研究中心 上海 200011
  • 收稿日期:2016-12-13 修回日期:2017-06-10 出版日期:2017-09-01 发布日期:2017-09-01
  • 通讯作者: 阮敏,副教授,博士,Email：doctorruanmin@hotmail.com
  • 作者简介:张煦,硕士,Email：ah_zhangxu@163.com
  • 基金资助:

    国家自然科学基金（81102049,81472517）; 上海市浦江人才计划（15PJD024）

Correlation between Toll-like receptor 9 and head and neck squamous cell carcinoma

Zhang Xu, Xu Enxin, Ruan Min.   

  1. Dept. of Oral and Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine;Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology;National Clinical Research Center of Stomatology, Shanghai 200011, China
  • Received:2016-12-13 Revised:2017-06-10 Online:2017-09-01 Published:2017-09-01
  • Supported by:

    ; This study was supported by National Natural Science Foundation of China(81102049, 81472517) and Shanghai Pujiang Program(15PJD024).

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摘要：

Toll样受体（TLR）9与特异性配体结合后,不仅在包括头颈鳞状细胞癌（HNSCC）在内的多种恶性肿瘤的发生发展中高表达,而且具有促进肿瘤细胞增殖、侵袭及转移的作用;但TLR9在一些肿瘤中高表达预示较高的术后复发率及较低的术后生存率,在另一些肿瘤中高表达却是肿瘤预后较好的分子指标。TLR9参与HNSCC的相关分子机制,在于促进细胞增殖、抑制程序性细胞死亡、调节血管新生、促进肿瘤侵袭和促进免疫逃逸。目前,基于TLR9的抗肿瘤治疗已被广泛用于临床,其最终的临床效果尚待进一步了解TLR9的表达调控,分析TLR9参与HNSCC的双刃剑作用机制及相关信号转导环节,开发特异性高、不良反应小和可有效用于临床的TLR9佐剂或抑制剂。

关键词: Toll样受体, Toll样配体, 表达, 头颈鳞状细胞癌

Abstract:

Chronic inflammation has close relation with the occurrence and development of malignant neoplasms, including head and neck squamous cell carcinoma(HNSCC). Toll-like receptor(TLR) may play an important role in this process. Toll-like receptor is a kind of the pattern recognition receptors which mediates the innate immune response by recognizing the pathogen-associated molecular pattern. High expression of TLR9 is found in some malignant neoplasms, including HNSCC, and has the ability to promote the proliferation, invasion and metastasis of tumor cells. As one of the key factors in the control network of the inflammation-related carcinogenesis, the potential molecular mechanism of TLR9 as well as the TLR9 based anti-tumor target therapy has been the hotspot in tumor research.

Key words: Toll like receptor, Toll like ligand, expression, head and neck squamous cell carcinoma

中图分类号: 

  • Q51
[1] Takeda K, Akira S. Toll-like receptors in innate immunity[J]. Int Immunol, 2005, 17(1):1-14.
[2] Dunne A, O’Neill LA. Adaptor usage and Toll-like receptor signaling specificity[J]. FEBS Lett, 2005, 579(15):3330-3335.
[3] Kelly JA, Moser KL, Harley JB. The genetics of systemic lupus erythematosus: putting the pieces to-gether[J]. Genes Immun, 2002, 3(Suppl 1):S71-S85.
[4] Hemmi H, Kaisho T, Takeda K, et al. The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets[J]. J Immunol, 2003, 170(6):3059-3064.
[5] Ishii KJ, Akira S. Innate immune recognition of, and regulation by, DNA[J]. Trends Immunol, 2006, 27 (11):525-532.
[6] Suwarti S, Yamazaki T, Svetlana C, et al. Recogni-tion of CpG oligodeoxynucleotides by human Toll-like receptor 9 and subsequent cytokine induction[J]. Biochem Biophys Res Commun, 2013, 430(4):1234- 1239.
[7] Lee JW, Choi JJ, Seo ES, et al. Increased Toll-like receptor 9 expression in cervical neoplasia[J]. Mol Carcinog, 2007, 46(11):941-947.
[8] Kotrashetti VS, Nayak R, Bhat K, et al. Immunohis-tochemical expression of TLR4 and TLR9 in various grades of oral epithelial dysplasia and squamous cell carcinoma, and their roles in tumor progression: a pilot study[J]. Biotech Histochem, 2013, 88(6):311- 322.
[9] Min R, Zun Z, Siyi L, et al. Increased expression of Toll-like receptor-9 has close relation with tumour cell proliferation in oral squamous cell carcinoma[J]. Arch Oral Biol, 2011, 56(9):877-884.
[10] Ali A, Natah S, Konttinen Y. Differential expression of Toll-like receptors in chronic hyperplastic candi-dosis[J]. Oral Microbiol Immunol, 2008, 23(4):299- 307.
[11] Zhang Y, Wang Q, Ma A, et al. Functional expre-ssion of TLR9 in esophageal cancer[J]. Oncol Rep, 2014, 31(5):2298-2304.
[12] Takala H, Kauppila JH, Soini Y, et al. Toll-like recep-tor 9 is a novel biomarker for esophageal squamous cell dysplasia and squamous cell carcinoma progre-ssion[J]. J Innate Immun, 2011, 3(6):631-638.
[13] Dai Q, Li XP, Chai L, et al. Polymorphisms of Toll-like receptor 9 are associated with nasopharyngeal carcinoma susceptibility[J]. Tumour Biol, 2014, 35(4):3247-3253.
[14] Merrell MA, Ilvesaro JM, Lehtonen N, et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity[J]. Mol Cancer Res, 2006, 4(7):437-447.
[15] Kauppila JH, Karttunen TJ, Saarnio J, et al. Short DNA sequences and bacterial DNA induce esophageal, gastric, and colorectal cancer cell invasion[J]. APMIS, 2013, 121(6):511-522.
[16] Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA[J]. Nature, 2000, 408(6813):740-745.
[17] Sheyhidin I, Nabi G, Hasim A, et al. Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma[J]. World J Gastroenterol, 2011, 17(32):3745-3751.
[18] Ruan M, Zhang Z, Li S, et al. Activation of Toll-like receptor-9 promotes cellular migration via up-regulating MMP-2 expression in oral squamous cell carcinoma[J]. PLoS One, 2014, 9(3):e92748.
[19] Wang C, Cao S, Yan Y, et al. TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients[J]. BMC Cancer, 2010, 10:415.
[20] Väisänen MR, Väisänen T, Jukkola-Vuorinen A, et al. Expression of toll-like receptor-9 is increased in poorly differentiated prostate tumors[J]. Prostate, 2010, 70(8):817-824.
[21] Tuomela J, Sandholm J, Karihtala P, et al. Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer[J]. Breast Cancer Res Treat, 2012, 135(2):481-493.
[22] Ronkainen H, Hirvikoski P, Kauppila S, et al. Absent Toll-like receptor-9 expression predicts poor prog-nosis in renal cell carcinoma[J]. J Exp Clin Cancer Res, 2011, 30:84.
[23] Kauppila JH, Takala H, Selander KS, et al. Increased Toll-like receptor 9 expression indicates adverse prognosis in oesophageal adenocarcinoma[J]. Histo-pathology, 2011, 59(4):643-649.
[24] Min R, Siyi L, Wenjun Y, et al. Toll-like receptor-9 agonists increase cyclin D1 expression partly through activation of activator protein-1 in human oral squa-mous cell carcinoma cells[J]. Cancer Sci, 2012, 103 (11):1938-1945.
[25] Schwartz C, Willebrand R, Huber S, et al. Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apo-ptosis[J]. Blood, 2015, 125(25):3896-3904.
[26] Belmont L, Rabbe N, Antoine M, et al. Expression of TLR9 in tumor-infiltrating mononuclear cells en-hances angiogenesis and is associated with a worse survival in lung cancer[J]. Int J Cancer, 2014, 134 (4):765-777.
[27] Di JM, Pang J, Sun QP, et al. Toll-like receptor 9 agonists up-regulates the expression of cyclooxyge-nase-2 via activation of NF-κB in prostate cancer cells[J]. Mol Biol Rep, 2010, 37(4):1849-1855.
[28] Ilvesaro JM, Merrell MA, Li L, et al. Toll-like receptor 9 mediates CpG oligonucleotide-induced cellular invasion[J]. Mol Cancer Res, 2008, 6(10): 1534-1543.
[29] Xue YW, Zhang QF, Zhu ZB, et al. Expression of cyclooxygenase-2 and clinicopathologic features in human gastric adenocarcinoma[J]. World J Gastroen-terol, 2003, 9(2):250-253.
[30] Ruan M, Thorn K, Liu S, et al. The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma[J]. Int J Oncol, 2014, 44(6):2103-2110.
[31] Weeratna RD, Bourne LL, Sullivan SM, et al. Com-bination of a new TLR9 agonist immunomodulator (CpG 7909) and paclitaxel for treatment of metasta-tic Lewis Lung Carcinoma(LLC)[J]. J Trans Edu, 2004, 3(3):271-288.
[32] Manegold C, Gravenor D, Woytowitz D, et al. Ran-domized phase Ⅱ trial of a Toll-like receptor 9 ago-nist oligodeoxynucleotide, PF-3512676, in combina-tion with first-line taxane plus platinum chemo-the-rapy for advanced-stage non-small-cell lung cancer [J]. J Clin Oncol, 2008, 26(24):3979-3986.
[33] Hirsh V, Paz-Ares L, Boyer M, et al. Randomized phase Ⅲ trial of paclitaxel/carboplatin with or without PF-3512676(Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer[J]. J Clin Oncol, 2011, 29(19):2667-2674.
[34] Chang LS, Leng CH, Yeh YC, et al. Toll-like recep-tor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy[J]. Mol Cancer, 2014, 13:60.
[35] Katsuda M, Iwahashi M, Matsuda K, et al. Peptide vaccine therapy with TLR-9 agonist for patients with esophageal squamous cell carcinoma[J]. Gan To Kagaku Ryoho, 2011, 38(12):1942-1944.
[36] Machiels JP, Kaminsky MC, Keller U, et al. Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck[J]. Invest New Drugs, 2013, 31(5):1207-1216.
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