a Centre for Chronic Diseases, College of Health and Biomedicine , Victoria University , Melbourne , Australia.
b Department of Medicine, Western Health, Faculty of Medicine, Dentistry and Health Sciences , The University of Melbourne, Regenerative Medicine and Stem Cells Program, Australian Institute of Musculoskeletal Sciences (AIMSS) , Melbourne , Australia.
Acta Oncol. 2018 Aug;57(8):1043-1056. doi: 10.1080/0284186X.2018.1429650. Epub 2018 Jan 25.
Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. Increased expression of the molecular target, EphB4 receptor, has been observed in several cancer types. However, studies on the role of EphB4 receptor in CRC have yielded contradictory results. The aim of this study was to investigate the influence of EphB4 expression levels on CRC cell behavior and its contribution to tumor growth and vascularization.
SW480, LIM2405 and CT26 CRC cell lines were transfected with EphB4 expression vector. High EphB4 expressing cells were compared to low EphB4 expressing empty vector controls. Proliferation and migration assays as well as EphrinB2-Fc cell stimulations were conducted in vitro and subcutaneous xenografts of CRC were analyzed in vivo.
High EphB4 expression enhanced migratory ability of these CRC cell lines in vitro and contributed to a significant increase in tumor growth and vascularization in vivo. Tumours induced with high EphB4 expressing SW480 and LIM2405 cells yielded homogenous masses densely packed with cancer cells. EphrinB2-Fc cell stimulations induced cell clustering of high EphB4 expressing SW480 and LIM2405 in vitro.
These results suggest that with enhanced vascularization and an increase in migratory abilities, the high EphB4 expressing cells may be able to metastasize more readily.
结直肠癌（CRC）是全球癌症相关死亡的最常见原因之一。已经在几种癌症类型中观察到分子靶标 EphB4 受体的表达增加。然而，EphB4 受体在 CRC 中的作用研究产生了相互矛盾的结果。本研究旨在探讨 EphB4 表达水平对 CRC 细胞行为的影响及其对肿瘤生长和血管生成的贡献。
SW480、LIM2405 和 CT26 CRC 细胞系用 EphB4 表达载体转染。高 EphB4 表达细胞与低 EphB4 表达空载体对照进行比较。在体外进行增殖和迁移测定以及 EphrinB2-Fc 细胞刺激，在体内分析 CRC 的皮下异种移植。
高 EphB4 表达增强了这些 CRC 细胞系的体外迁移能力，并导致体内肿瘤生长和血管生成的显著增加。用高 EphB4 表达的 SW480 和 LIM2405 细胞诱导的肿瘤产生了癌细胞密集堆积的均匀肿块。EphrinB2-Fc 细胞刺激在体外诱导高 EphB4 表达的 SW480 和 LIM2405 的细胞聚集。
这些结果表明，随着血管生成的增强和迁移能力的提高，高 EphB4 表达的细胞可能更容易转移。
