Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer

详细信息    查看全文

• 作者：Myung Ah Lee (14)
  Jin-Hee Park (14)
  Si Young Rhyu (14)
  Seong-Taek Oh (15)
  Won-Kyoung Kang (15)
  Hee-Na Kim (16)
  
• 关键词：Wnt3a ; Wnt5a ; MMP ; 9 ; VEGFR ; 2 ; β ; catenin ; Colorectal cancer
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：426 KB
• 参考文献：1. Jung KW, Park SH, Won YJ, Kong YJ, Lee JY, Park EC, Lee JS: Prediction of cancer incidence and mortality in Korea. / Cancer Res Treat 2011,43(1):12-8. CrossRef
  2. Polarkis P: Wnt signaling and cancer. / Genes Dev 2000, 14:1837-851.
  3. Saif MW, Chu E: Biology of colorectal cancer. / Cancer J 2010,16(3):196-01. CrossRef
  4. Huang D, Du X: Crosstalk between tumor cells and microenvironment via wnt pathway in colorectal cancer dissemination. / J Gastroenterol 2008,14(12):1823-827.
  5. Katoh M: WNT/PCP signaling pathway and human cancer (review). / Oncol Repub 2005,14(6):1583-588.
  6. McDonald SL, Silver A: The opposing roles of wnt-5a in cancer. / Br J Can 2009, 101:209-14. CrossRef
  7. Dejimek J, Dejimek A, S?fholm A, Sj?lander A, Andersson T: Wnt-5a protein expression in primary dukes B colon cancers identifies a subgroup of patients with good prognosis. / Cancer Res 2005,65(20):9142-146. CrossRef
  8. Rawson JB, Mrkonjic M, Daftary D, Dicks E, Buchanan DD, Younghusband HB, Parfrey PS, Young JP, Pollett A, Green RC, Gallinger S, McLaughlin JR, Knight JA, Bapat B: Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients. / Br J Cancer 2011,104(12):1906-912. CrossRef
  9. Ingraham CA, Park GC, Makarenkova HP, Crossin K: Matrix Metalloproteinase (MMP)-9 induced by wnt signaling increases the proliferation and migration of embryonic neural stem cells at low O2 levels. / J Bio Chem 2011,286(20):17649-7657. CrossRef
  10. Karow M, Popp T, Egea V, Ries C, Jochum M, Neth P: Wnt signaling in muse mesenchymal stem cells: impact on proliferation, invasion and MMP expression. / J Cell Mol Med 2009,13(88):2506-520. CrossRef
  11. Bendardaf R, Buhmeida A, Hilska M, Laato M, Syrj?nen S, Syrj?nen K, Collan Y, Pyrh?nen S: MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. / Cancer Invest 2010,28(1):38-3. CrossRef
  12. Lee MA, Park KS, Lee HJ, Jung JH, Kang JH, Hong YS, Lee KS, Kim DG, Kim SN: Survivin expression and its clinical significance in pancreatic cancer. / BMC Cancer 2005, 5:127-32. CrossRef
  13. Neth P, Ciccarella M, Egea V, Hoelters J, Jochum M, Ries C: Wnt signaling regulates the invasion capacity of human mesenchymal stem cells. / Stem Cells 2006,24(8):1892-903. CrossRef
  14. Elzagheid A, Buhmeida A, Korkeila E, Collan Y, Syrjanen K, Pyrhonen S: Nuclear beta-catenin expression as a prognostic factor in advanced colorectal carcinoma. / World J Gastroenterol 2008,14(24):3866-871. CrossRef
  15. Suzuki H, Masuda N, Shimura T, Araki K, Kobayashi T, Tsutsumi S, Asao T, Kuwano H: Nuclear beta-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma. / Anticancer Res 2008,28(3B):1821-830.
  16. Kahlil S, Tan GA, Giri DD, Zou XK, Howe LR: Activation status of Wnt/β-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse. / PLos One 2012,7(3):e33421. CrossRef
  17. Moyes LH, McEwan H, Radulescu S, Pawlikowski J, Lamm CG, Nixon C, Sansom OJ, Going JJ, Fullarton GM, Adams PD: Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus. / J Pathol 2012,228(1):99-12.
  18. Voloshanenko O, Erdmann G, Dubashi TD, Augustin I, Metzig M, Moffa G, Hundsrucker C, Ken G, Sandmann T, Anchang B, Demir K, Boehm C, Leible S, Ball CR, Glimm H, Spang R, Boutros M: Wnt secretion is required to maintain high levels of wnt activity in colon cancer cells. / Nat Commun 2013, 4:2610. CrossRef
  19. Cheung LW, Leung PC, Wong AS: Gonadotropin-releasing hormone promotes ovarian cancer cell invasiveness through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase (MMP)-2 and MMP-9. / Cancer Res 2006,66(22):10902-0910. CrossRef
  20. Roh SA, Choi EY, Cho DH, Jang SJ, Kim SY, Kim YS, Kim JC: Growth and invasion of sporadic colorectal adenocarcinomas in terms of genetic change. / J Korean Med Sci 2010, 25:353-60. CrossRef
  21. Song KS, Li G, Kim JS, Jing K, Kim TD, Kim JP, Seo SB, Yoo JK, Park HD, Hwang BD, Lim K, Yoon WH: Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells. / BMC Cancer 2011, 11:307. CrossRef
  22. Singh T, Katiyar SK: Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE2-Mediated Activation of β-Catenin Signaling. / PLos One 2013,8(3):e60749. CrossRef
  23. Naik S, Dotharger RS, Marasa J, Lewis CL, Piwnica-Worms D: Vascular endothelial growth factor receptor-1 is synthetic lethal to aberrant beta catenin activation in colon cancer. / Clin Cancer Res 2009,15(24):7529-537. CrossRef
  24. Zeitlin BD, Ellis LM, Nor JE: Inhibition of vascular endothelial growth factor receptor-1/wnt beta catenin cross talk leads to tumor cell death. / Clin Cancer Res 2009,15(24):7453-455. CrossRef
  25. Yoshihara T, Takahashi-Yanaga F, Shiraishi F, Morimoto S, Watanabe Y, Hirata M, Hoka S, Sasaguri T: Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway. / Mol Cancer 2010,16(9):245. CrossRef
  26. Kin JU, Bae BN, Kim HJ, Park KM: Prognostic significance of epidermal growth factor receptor and vascular endothelial growth factor receptor in colorectal adenocarcinoma. / APMIS 2011,119(7):449-59. CrossRef
  27. Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A, Asahara T, Yasui W, Kikuchi A: Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. / Cancer Res 2006,66(21):10439-0448. CrossRef
  28. Pukrop T, Klemm F, Hagemann T, Gradl D, Schulz M, Siemes S, Trümper L, Binder C: Wnt5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. / Proc Natl Acad Sci U S A 2006,103(14):5454-459. CrossRef
  29. Ying J, Li H, Yu J, Ng KM, Poon FF, Wong SC, Chan AT, Sung JJ, Tao Q: WNT5A exhibits tumor-suppressive activity through antagonizing the Wnt/beta-catenin signaling, and is frequently methylated in colorectal cancer. / Clin Cancer Res 2008,14(1):55-1. CrossRef
  30. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/14/125/prepub
  
• 作者单位：Myung Ah Lee (14)
  Jin-Hee Park (14)
  Si Young Rhyu (14)
  Seong-Taek Oh (15)
  Won-Kyoung Kang (15)
  Hee-Na Kim (16)
  
  14. Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, 222 Banpo-daero, Seocho-gu, 137-701, Seoul, Korea
  15. Department of Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
  16. Department of Pathology, Seoul Clinical Laboratory Clinic, Seoul, Korea
  
• ISSN：1471-2407

文摘

Background The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). Methods Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2. Results Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p--.038) and MMP-9 expression in the primary tumor (p--.0387), mesenchyme adjacent to tumor (p--.022) and metastatic site (p--.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p--.05). Conclusions Wnt3a and wnt5a expression had a concordance rate higher than 60% with a high concordance rate between the primary tumor and metastatic site. Wnt3a expression is associated with the expression of MMP-9 in primary tumor tissue adjacent mesenchymal tissue, and at the metastatic site. As a prognostic marker, only β-catenin expression showed significant relation with survival outcome.