EphB4 promotes the proliferation, invasion, and angiogenesis of human colorectal cancer

被引:39
作者
Lv, JingHuan [1 ,2 ]
Xia, QiuYuan [1 ]
Wang, JianJun [1 ]
Shen, Qin [1 ]
Zhang, Jin [1 ]
Zhou, XiaoJun [1 ]
机构
[1] Nanjing Univ, Sch Med, Jinling Hosp, Dept Pathol, Nanjing 210002, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Suzhou Hosp Affiliated, Suzhou Municipal Hosp, Dept Pathol, Suzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Angiogenesis; Colorectal cancer; EphB4; Invasion; Proliferation; MICROVESSEL DENSITY; RECEPTOR; EXPRESSION; EPHRIN; PROGRESSION; CARCINOMA; PATTERNS; LIGANDS;
D O I
10.1016/j.yexmp.2016.03.011
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Objective: Eph/Ephrin signalling plays an important role in tumorigenesis, neovascularization, and vasculogenesis. However, studies concerning the role of EphB4 in colorectal cancer (CRC) show inconsistent results, and the function of EphB4 in the formation of CRC-related blood vessels is not fully understood. The aim of this study is to investigate the EphB4 expression in CRC and the role of EphB4 in tumour angiogenesis. Materials and methods: EphB4 and EphrinB2 expressions were detected in 200 CRC samples and 50 paired colorectal mucosae by immunohistochemistry. Xenograft animal models were established by stable knockdown and stable overexpression of EphB4, and control cell lines were used to investigate the role of EphB4 in CRC. Microvessels were stained with anti-CD34, and microvessel density (MVD) was assessed. Results: EphB4 protein was more highly expressed in CRC tissues compared with adjacent normal mucosae (P < 0.05), while EphrinB2 levels were unchanged. Modulation of EphB4 levels in colon cancer cell line SW480 resulted in significant effects on tumour growth and invasion in vivo, with stable overexpression of EphB4 associated with faster growth and invasion. Furthermore, microvessel density values in xenograft tumours were significantly correlated with EphB4 (P < 0.05). Conclusion: EphB4 acts as a tumour promoter associated with proliferation, invasion, and angiogenesis, and may be used as a potential CRC therapeutic target. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:402 / 408
页数:7
相关论文
共 25 条
[1]  
[Anonymous], COLD SPRING HARB PER
[2]   Ephrin B2 and EphB4 selectively mark arterial and venous vessels in cerebral arteriovenous malformation [J].
Bai, Jie ;
Wang, Ya-jie ;
Liu, Li ;
Zhao, Yuan-li .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2014, 42 (02) :405-415
[3]   EphB receptor activity suppresses colorectal cancer progression [J].
Batlle, E ;
Bacani, J ;
Begthel, H ;
Jonkeer, S ;
Gregorieff, A ;
van de Born, M ;
Malats, N ;
Sancho, E ;
Boon, E ;
Pawson, T ;
Gallinger, S ;
Pals, S ;
Clevers, H .
NATURE, 2005, 435 (7045) :1126-1130
[4]   EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma [J].
Becerikli, M. ;
Merwart, B. ;
Lam, M. C. ;
Suppelna, P. ;
Rittig, A. ;
Mirmohammedsadegh, A. ;
Stricker, I. ;
Theiss, C. ;
Singer, B. B. ;
Jacobsen, F. ;
Steinstraesser, L. .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (08) :1781-1791
[5]   Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome [J].
Brantley-Sieders, Dana M. ;
Jiang, Aixiang ;
Sarma, Krishna ;
Badu-Nkansah, Akosua ;
Walter, Debra L. ;
Shyr, Yu ;
Chen, Jin .
PLOS ONE, 2011, 6 (09)
[6]   EPHB4 and survival of colorectal cancer patients [J].
Davalos, Veronica ;
Dopeso, Higinio ;
Castano, Julio ;
Wilson, Andrew J. ;
Vilardell, Felip ;
Romero-Gimenez, Jordi ;
Espin, Eloy ;
Armengol, Manel ;
Capella, Gabriel ;
Mariadason, John M. ;
Aaltonen, Lauri A. ;
Schwartz, Simo, Jr. ;
Arango, Diego .
CANCER RESEARCH, 2006, 66 (18) :8943-8948
[7]   The Receptor Tyrosine Kinase EPHB4 Has Tumor Suppressor Activities in Intestinal Tumorigenesis [J].
Dopeso, Higinio ;
Mateo-Lozano, Silvia ;
Mazzolini, Rocco ;
Rodrigues, Paulo ;
Lagares-Tena, Laura ;
Ceron, Julian ;
Romero, Jordi ;
Esteves, Marielle ;
Landolfi, Stefania ;
Hernandez-Losa, Javier ;
Castano, Julio ;
Wilson, Andrew J. ;
Ramon Y Cajal, Santiago ;
Mariadason, John M. ;
Schwartz, Simo, Jr. ;
Arango, Diego .
CANCER RESEARCH, 2009, 69 (18) :7430-7438
[8]   The EphB4 Receptor Tyrosine Kinase Promotes Lung Cancer Growth: A Potential Novel Therapeutic Target [J].
Ferguson, Benjamin D. ;
Liu, Ren ;
Rolle, Cleo E. ;
Tan, Yi-Hung Carol ;
Krasnoperov, Valery ;
Kanteti, Rajani ;
Tretiakova, Maria S. ;
Cervantes, Gustavo M. ;
Hasina, Rifat ;
Hseu, Robyn D. ;
Iafrate, A. John ;
Karrison, Theodore ;
Ferguson, Mark K. ;
Husain, Aliya N. ;
Faoro, Leonardo ;
Vokes, Everett E. ;
Gill, Parkash S. ;
Salgia, Ravi .
PLOS ONE, 2013, 8 (07)
[9]   Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505 [J].
Foote, RL ;
Weidner, N ;
Harris, J ;
Hammond, E ;
Lewis, JE ;
Vuong, T ;
Ang, KK ;
Fu, KK .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2005, 61 (03) :745-753
[10]   Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours [J].
Guo, DL ;
Zhang, J ;
Yuen, ST ;
Tsui, WY ;
Chan, ASY ;
Ho, C ;
Ji, JF ;
Leung, SY ;
Chen, X .
CARCINOGENESIS, 2006, 27 (03) :454-464