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学科主题: 临床医学
题名:
Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours
作者: Guo, DL; Zhang, J; Yuen, ST; Tsui, WY; Chan, ASY; Ho, C; Ji, JF; Leung, SY; Chen, X
刊名: CARCINOGENESIS
发表日期: 2006-03-01
DOI: 10.1093/carcin/bgi259
卷: 27, 期:3, 页:454-464
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: RECEPTOR TYROSINE KINASE ; DOWN-REGULATION ; BETA-CATENIN ; CANCER ; CARCINOMA ; MIGRATION ; FAMILY ; APC ; IDENTIFICATION ; TUMORIGENESIS
英文摘要:

EphB2, a receptor tyrosine kinase regulated by the beta-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the Apc(Min/+) mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P = 0.005), poor differentiation (P < 0.001), poor overall survival (P = 0.005) and disease-free survival (P = 0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration.

语种: 英语
WOS记录号: WOS:000235771300011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65926
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
2.Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
3.Peking Univ, Beijing Canc Hosp, Dept Surg, Beijing 100871, Peoples R China

Recommended Citation:
Guo, DL,Zhang, J,Yuen, ST,et al. Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours[J]. CARCINOGENESIS,2006,27(3):454-464.
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