Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients
详细信息 查看全文
- 作者：Yanyang Tu (1)
Shiming He (2)
Jianfang Fu (3)
Gang Li (2)
Ruxiang Xu (4)
Hongliu Lu (4)
Jianping Deng (2) - 关键词：Glioma ; EphrinB2 ; Immunohistochemistry ; EphB4 ; Prognosis
- 刊名：Clinical and Translational Oncology
- 出版年：2012
- 出版时间：March 2012
- 年：2012
- 卷：14
- 期：3
- 页码：214-220
- 全文大小：384KB
- 参考文献：1. Rainov NG, Heidecke V (2011) Clinical development of experimental therapies for malignant glioma. Sultan Qaboos Univ Med J 11:5鈥?8
2. Kleihues P, Sobin LH (2000) World Health Organization classification of tumors. Cancer 88:2887 CrossRef
3. Pasquale EB (1997) The Eph family of receptors. Curr Opin Cell Biol 9:608鈥?15 CrossRef
4. Maekawa H, Oike Y, Kanda S et al (2003) EphrinB2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature. Arterioscler Thromb Vasc Biol 23:2008鈥?014 CrossRef
5. Das A, Shergill U, Thakur L et al (2010) Ephrin B2/EphB4 pathway in hepatic stellate cells stimulates Erk-dependent VEGF production and sinusoidal endothelial cell recruitment. Am J Physiol Gastrointest Liver Physiol 298:G908鈥揋915 CrossRef
6. Xia G, Kumar SR, Masood R et al (2005) EphB4 expression and biological significance in prostate cancer. Cancer Res 65:4623鈥?632 CrossRef
7. Noren NK, Lu M, Freeman AL et al (2004) Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci USA 101:5583鈥?588 CrossRef
8. Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signaling. Nat Rev Mol Cell Biol 3:475鈥?86 CrossRef
9. Fox BP, Kandpal RP (2004) Invasiveness of breast carcinoma cells and transcript profile: Eph receptors and ephrin ligands as molecular markers of potential diagnostic and prognostic application. Biochem Biophys Res Commun 318:882鈥?92 CrossRef
10. Tang XX, Brodeur GM, Campling BG et al (1999) Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma. Clin Cancer Res 5:455鈥?60
11. Tang XX, Jhao H, Robinson ME et al (2000) Implication of EPHB6, EFNB2 and EFNB3 expression in human neuroblastoma. Proc Natl Acad Sci U S A 97:10936鈥?0941 CrossRef
12. Martiny-Baron G, Holzer P, Billy E et al (2010) The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis. Angiogenesis 13: 259鈥?67 CrossRef
13. Branco-Price C, Johnson RS (2010) Tumor vessels are Eph-ing complicated. Cancer Cell 17:533鈥?34 CrossRef
14. Kumar SR, Scehnet JS, Ley EJ et al (2009) Preferential induction of EphB4 over EphB2 and its implication in colorectal cancer progression. Cancer Res 69:3736鈥?745 CrossRef
15. Pennisi A, Ling W, Li X et al (2009) The ephrinB2/ EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood 114:1803鈥?812 CrossRef
16. H茅roult M, Schaffner F, Pfaff D et al (2010) EphB4 promotes site-specific metastatic tumor cell dissemination by interacting with endothelial cellexpressed ephrinb2. Mol Cancer Res 8:1297鈥?309 CrossRef
17. Xue C, Huang Z, Wang J et al (2009) EphrinB2 and EphB4 expression in pterygia: new insights and preliminary results. Can J Ophthalmol 44:185鈥?88 CrossRef
18. Yamanda S, Ebihara S, Asada M et al (2009) Role of ephrinB2 in nonproductive angiogenesis induced by Delta-like 4 blockade. Blood 113:3631鈥?639 CrossRef
19. Alam SM, Fujimoto J, Jahan I et al (2007) Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers. Ann Oncol 18:485鈥?90 CrossRef
20. Alam SM, Fujimoto J, Jahan I et al (2009) Coexpression of EphB4 and ephrinB2 in tumor advancement of uterine cervical cancers. Gynecol Oncol 114:84鈥?8 CrossRef
21. McCarty KS Jr, Miller LS, Cox EB et al (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109:716鈥?21
22. Catt SL, Anderson JL, Critchley GR (2011) Patients鈥?and staff鈥檚 experiences of multidisciplinary follow-up for high-grade glioma after radical radiotherapy. Psychol Health Med 16:357鈥?65 CrossRef
23. Walbert T, Mikkelsen T (2011) Recurrent highgrade glioma: a diagnostic and therapeutic challenge. Expert Rev Neurother 11:509鈥?18 CrossRef
24. Batlle E, Bacani J, Begthel H et al (2005) Ephb receptor activity suppresses colorectal cancer progression. Nature 435:1126鈥?130 CrossRef
25. Wu D, Suo Z, Kristensen GB et al (2004) Prognostic value of epha2 and ephrina-1 in squamous cell cervical carcinoma. Gynecol Oncol 94:312鈥?19 CrossRef
26. Wu Q, Suo Z, Risberg B et al (2004) Expression of ephb2 and ephb4 in breast carcinoma. Pathol Oncol Res 10:26鈥?3 CrossRef
27. Xia G, Kumar SR, Stein JP et al (2006) EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival. Oncogene 25:769鈥?80 CrossRef
28. Masood R, Kumar SR, Sinha UK et al (2006) EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. Int J Cancer 119:1236鈥?248 CrossRef
29. Kumar SR, Singh J, Xia G et al (2006) Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol 169:279鈥?93 CrossRef
30. Yavrouian EJ, Sinha UK, Rice DH et al (2008) The significance of EphB4 and EphrinB2 expression and survival in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 134:985鈥?91 CrossRef
31. Ozg眉r E, Heidenreich A, Dagtekin O et al (2011) Distribution of EphB4 and EphrinB2 in normal and malignant urogenital tissue. Urol Oncol 29:78鈥?4 CrossRef
32. Krasnoperov V, Kumar SR, Ley E et al (2010) Novel EphB4 monoclonal antibodies modulate angiogenesis and inhibit tumor growth. Am J Pathol 176:2029鈥?038 CrossRef
33. Erber R, Eichelsbacher U, Powajbo V et al (2006) EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J 25:628鈥?41 CrossRef - 作者单位：Yanyang Tu (1)
Shiming He (2)
Jianfang Fu (3)
Gang Li (2)
Ruxiang Xu (4)
Hongliu Lu (4)
Jianping Deng (2)
1. Department of Emergency, Tangdu Hospital, Fourth Military Medical University, Xi鈥檃n, 710038, China
2. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi鈥檃n, 710038, China
3. Department of Endocrine, Xijing Hospital, Fourth Military Medical University, Xi鈥檃n, 710032, China
4. Department of Neurosurgery, General Hospital of Beijing Military Zone, Beijing, 100041, China
文摘
Objective The ligand EphrinB2 and the corresponding receptor EphB4 are up-regulated and involved in tumour growth in various human cancers. However, little is known about how this receptor-ligand complex contributes to the progression of glioma. This prompted us to study the association between the expressions of EphrinB2 and EphB4, clinicopathological variables, and glioma patient outcome. Methods Immunohistochemical staining was performed to detect the expression patterns of EphrinB2 and EphB4 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Results Immunohistochemical analysis revealed that the expression of EphrinB2 was significantly correlated with that of EphB4 (r=0.86, p=0.002). EphrinB2 and EphB4 were significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization grades of patients with gliomas, respectively. Especially, the positive expression rates of EphrinB2 and EphB4 were significantly higher in patients with higher grade (both p=0.001) and lower KPS score (p=0.002 and 0.003, respectively). Multivariate Cox regression analysis revealed that EphrinB2 and EphB4 expressions were both independent prognostic factors for progress-free survival of glioblastoma patients (both p=0.02). Conclusion Our data indicated for the first time that EphrinB2 and EphB4 expressions increase according to the histopathological grade and KPS score of glioma, and their expression levels are related to the progression-free survival of glioblastoma patients.