Nuclear expression of CXCR4 is associated with advanced colorectal cancer

Nuclear expression of CXCR4 is associated with advanced colorectal cancer
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DOI:
10.1007/s00384-010-0999-1
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发表时间:
2010-10-01
影响因子:
2.8
通讯作者:
Chang, Shih-Ching
Chang, Shih-Ching
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Shang-Chiung;Lin, Jen-Kou;Chang, Shih-Ching

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CXCR 4及其配体SDF-1 α在结肠癌的靶向转移中发挥重要作用。本研究以台北荣民总医院自2000年至2004年共388例大肠癌患者为研究对象,分析大肠癌组织中CXCR 4的表达,并探讨SDF-1 α对大肠癌细胞CXCR 4表达的影响。通过免疫组织化学(抗CXCR 4 mAb,R&D 12 G5)观察CRC中CXCR 4的表达。用SDF-1 α体外处理HCT 116、SW 480和SW 620细胞,用Western blotting分析CXCR 4蛋白在细胞质和细胞核中的表达,结果显示CXCR 4在大肠癌细胞质和细胞核中的表达率分别为35.6%和36.9%。CXCR 4在细胞核而非细胞质中的表达与晚期结直肠癌和淋巴管浸润有关(p < 0.001)。然而,在多变量分析中,CXCR 4的核表达与患者的预后无关。在体外研究中,SDF-1 α刺激三种结直肠癌细胞系可增强CXCR 4核表达,CXCR 4的表达在CRC进展中起作用,可能与SDF-1 α刺激有关。
CXCR4 and its ligand, SDF-1 alpha, play an important role in the targeted metastasis of colon cancer. In this study, we analyzed an expression of CXCR4 in clinical samples and showed that SDF-1 alpha affected the expression of CXCR4 in colon cancer cells.A total of 388 patients with colorectal cancer (CRC) who underwent surgery in Taipei Veterans General Hospital from 2000 to 2004 were included. The expression of CXCR4 in CRC was visualized by immunohistochemistry (anti-CXCR4 mAb, R&D 12G5). HCT116, SW480, and SW620 cells were treated with SDF-1 alpha in vitro and the CXCR4 proteins located in the cytoplasmic and nuclear compartments were separated and analyzed with western blotting.The frequency of cytoplasmic and nuclear expression of CXCR4 in colorectal cancers was 35.6% and 36.9%, respectively. Nuclear but not cytoplasmic expression of CXCR4 was associated with advanced CRC (p < 0.001) and lymphovascular invasion. However, in multivariate analysis, nuclear expression of CXCR4 did not correlate with patients' outcome. In the in vitro study, SDF-1 alpha, stimulation of three colorectal carcinoma lines enhanced the CXCR4 nuclear expression.Expression of the CXCR4 plays a role in CRC progression and may be associated with SDF-1 alpha stimulation.