Expression and significance of the TLR4/MyD88 signaling pathway in ovarian epithelial cancers

详细信息    查看全文

• 作者：Ki Hyung Kim (1) (2)
  Moo Sung Jo (3)
  Dong Soo Suh (1) (2)
  Man Soo Yoon (1) (2)
  Dong Hun Shin (4) (5)
  Jeong Hee Lee (4)
  Kyung Un Choi (4) (5)
  
• 关键词：Toll ; like receptor ; MyD88 ; Ovarian epithelial cancer
• 刊名：World Journal of Surgical Oncology
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：10
• 期：1
• 全文大小：808KB
• 参考文献：1. Yu L, Chen S: Toll-like receptors expressed in tumor cells: Targets for therapy. / Cancer Immunol Immunother 2008, 57:1271-278. CrossRef
  2. Huang B, Zhao J, Unkeless JC, Feng ZH, Xiong H: TLR signaling by tumor and immune cells: A double-edged sword. / Oncogene 2008, 27:218-24. CrossRef
  3. Rakoff-Nahoum S, Medzhitov R: Toll-like receptors and cancer. / Nat Rev Cancer 2009, 9:57-3. CrossRef
  4. Akira S: Toll-like receptor signaling. / J Biol Chem 2003, 278:38105-8108. CrossRef
  5. Naugler WE, Sakurai T, Kim S, Maeda S, Kim A, Elsharkawy AM, Karin M: Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. / Science 2007, 317:121-24. CrossRef
  6. Rakoff-Nahoum S, Medzhitov R: Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. / Science 2007, 317:124-27. CrossRef
  7. Fukata M, Abreu MT: Role of toll-like receptors in gastrointestinal malignancies. / Oncogene 2008, 27:234-43. CrossRef
  8. Yu L, Wang L, Chen S: Toll-like receptors, inflammation and tumor in the human female reproductive tract. / Am J Reprod Immunol 2009, 62:1-. CrossRef
  9. Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G: TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. / Cancer Res 2006, 66:3859-868. CrossRef
  10. Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G: Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. / Cancer Res 2000, 60:4693-696.
  11. Zhang JJ, Wu HS, Wang L, Tian Y, Zhang JH, Wu HL: Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma. / World J Gastroenterol 2010, 16:2881-888. CrossRef
  12. Cheng I, Plummer SJ, Casey G, Witte JS: Toll-like receptor 4 genetic variation and advanced prostate cancer risk. / Cancer Epidemiol Biomarkers Prev 2007, 16:352-55. CrossRef
  13. Song C, Chen LZ, Zhang RH, Yu XJ, Zeng YX: Functional variant in the 3'-untranslated region of toll-like receptor 4 is associated with nasopharyngeal carcinoma risk. / Cancer Biol Ther 2006, 5:1285-291. CrossRef
  14. El-Omar EM, Ng MT, Hold GL: Polymorphisms in toll-like receptor genes and risk of cancer. / Oncogene 2008, 27:244-52. CrossRef
  15. Wang EL, Qian ZR, Nakasono M, Tanahashi T, Yoshimoto K, Bando Y, Kudo E, Shimada M, Sano T: High expression of toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. / Br J Cancer 2010, 102:908-15. CrossRef
  16. Zhou M, McFarland-Mancini MM, Funk HM, Husseinzadeh N, Mounajjed T, Drew AF: Toll-like receptor expression in normal ovary and ovarian tumors. / Cancer Immunol Immunother 2009, 58:1375-385. CrossRef
  17. Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T, Suzuki M, Sato I, Taguchi K: Clinical characteristics of clear cell carcinoma of the ovary: A distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. / Cancer 2000, 88:2584-589. CrossRef
  18. Itamochi H, Kigawa J, Terakawa N: Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. / Cancer Sci 2008, 99:653-58. CrossRef
  19. Itamochi H, Kigawa J, Sultana H, Iba T, Akeshima R, Kamazawa S, Kanamori Y, Terakawa N: Sensitivity to anticancer agents and resistance mechanisms in clear cell carcinoma of the ovary. / Jpn J Cancer Res 2002, 93:723-28. CrossRef
  20. Xu Z, Chen ZP, Malapetsa A, Alaoui-Jamali M, Bergeron J, Monks A, Myers TG, Mohr G, Sausville EA, Scudiero DA, Aloyz R, Panasci LC: DNA repair protein levels vis-a-vis anticancer drug resistance in the human tumor cell lines of the national cancer institute drug screening program. / Anticancer Drugs 2002, 13:511-19. CrossRef
  21. Karin M: Nuclear factor-kappaB in cancer development and progression. / Nature 2006, 441:431-36. CrossRef
  22. Annunziata CM, Stavnes HT, Kleinberg L, Berner A, Hernandez LF, Birrer MJ, Steinberg SM, Davidson B, Kohn EC: Nuclear factor kappaB transcription factors are coexpressed and convey a poor outcome in ovarian cancer. / Cancer 2010, 116:3276-284. CrossRef
  
• 作者单位：Ki Hyung Kim (1) (2)
  Moo Sung Jo (3)
  Dong Soo Suh (1) (2)
  Man Soo Yoon (1) (2)
  Dong Hun Shin (4) (5)
  Jeong Hee Lee (4)
  Kyung Un Choi (4) (5)
  
  1. Department of Obstetrics and Gynecology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea
  2. Biomedical Research Institute and Pusan Cancer Center, Pusan National University Hospital, Busan, Korea
  3. Department of Medicine School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea
  4. Department of Pathology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea
  5. Department of Pathology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea
  

文摘

Background Toll-like receptors (TLR) are a family of pattern recognition receptors that constitutes a major part of the innate immune system. The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects. Methods To demonstrate the role of TLR4/MyD88 signaling in ovarian epithelial cancers (OECs), we examined the expression of TLR4, MyD88 and nuclear factor- κB (NF-κB) in OECs. The expression of TLR4, MyD88, and NF-κB was detected by immunohistochemistry, and the relationships between these and clinicopathologic features in 123 cases of OECs were also analyzed. Results The expression of TLR4, MyD88, and NF-κB in OECs was observed in 46.3% (57/123), 36.6% (45/123) and 65% (80/123) of OEC cases, respectively. The TLR4, MyD88, and NF-κB expressions were associated with the histologic type of OECs, particularly with the clear cell type of OEC. There was no significant correlation between TLR4 or NF-κB expression and histologic grade, tumor size, mitotic count, FIGO (International Federation of Gynecology and Obstetrics) stage, disease recurrence. However, there was a significant correlation between MyD88 expression and FIGO stage, disease recurrence as well as histologic type. In univariate analysis, the expression of TLR4 and MyD88, and the coexpression of TLR4/MyD88 and TLR4/MyD88/NF-κB had a significant impact on the survival of patients with OECs. Only MyD88 expression had an independent prognostic significance in multivariate analysis. Conclusions Our findings suggest that the TLR4/MyD88 signaling pathway is associated with the survival of patients with OECs, and that MyD88 is an independent prognostic predictor in patients with OECs. The TLR4/MyD88 signaling pathway may be a mechanism responsible for poor prognosis in patients with clear cell type of OEC.