CXCR4 expression is associated with pelvic lymph node metastasis in cervical adenocarcinoma
CXCR4 expression is associated with pelvic lymph node metastasis in cervical adenocarcinoma
复制标题
DOI：
10.1111/j.1525-1438.2007.00841.x
复制
发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Chen, C. -P.
中科院分区：
文献类型：
--
作者：
Yang, Y. -C.;Lee, Z. -Y.;Chen, C. -P.
本研究旨在探讨CXCR 4受体在宫颈腺癌中的表达及其与盆腔淋巴结转移的关系。采用免疫组化法评价CXCR 4的表达与临床IB期宫颈腺癌（n = 37）和其他原因子宫切除术后获得的良性标本（n = 48）存档组织中盆腔淋巴结转移的相关性。使用表达CXCR 4的HeLa细胞（宫颈腺癌衍生细胞）系来研究CXCR 4受体与基质细胞衍生因子1 α（SDF-1 α）之间的相互作用。采用细胞迁移实验、细胞计数、流式细胞术、细胞增殖实验和western blot等方法研究CXCR 4的功能及其下游信号转导。阳性病例根据其染色情况半定量地分为三个评分等级。CXCR 4强阳性者盆腔淋巴结转移率明显高于CXCR 4弱阳性或阴性者（87.5%vs34.5%，P = 0.014）。只有25%的良性标本CXCR 4染色弱或阴性。功能性CXCR 4受体在HeLa细胞上表达。SDF-1 α引起了重要的信号转导事件，包括趋化性和凋亡的拯救。这些行动显然介导的细胞外信号调节激酶1/2和AKT途径的激活和磷酸化。我们的结论是CXCR 4表达与宫颈腺癌细胞的迁移和增殖有关，表达CXCR 4的原发性宫颈腺癌细胞更容易转移到盆腔淋巴结。
The aim of this study is to investigate the expression of CXCR4 receptor in cervical adenocarcinoma and related mechanisms involved in pelvic lymph node metastasis. Immunohistochemistry was used to evaluate the expression of CXCR4 and the association of pelvic lymph node metastasis in archived tissue from clinical stage IB cervical adenocarcinomas (n = 37) and from benign specimens obtained at hysterectomy for other causes (n = 48). The HeLa cell (cervical adenocarcinoma-derived cell) line that expresses CXCR4 was used to study the interaction between the CXCR4 receptor and stromal cell-derived factor 1 alpha (SDF-1 alpha). Cell migration assays, cell numbers, flow cytometry, cell proliferation assay, and western blot were used to study the function of CXCR4 and its downstream signal transduction. The positive cases were semiquantitatively divided into three score classes according to their staining. Tumors with strong CXCR4 stainings were more likely to have pelvic lymph node metastasis than those with weak or negative stainings (87.5% vs 34.5%; P = 0.014). Only 25% of the benign specimens had weak or negative staining for CXCR4. Functioning CXCR4 receptor was expressed on HeLa cells. SDF-1 alpha provoked significant signal transduction events, including chemotaxis and rescue from apoptosis. These actions were apparently mediated by the activation and phosphorylation of the extracellular signal-regulated kinase 1/2 and AKT pathways. We conclude CXCR4 expression is associated with cervical adenocarcinoma cell migration and proliferation, and primary cervical adenocarcinoma cells expressing CXCR4 are significantly more likely to metastasize to pelvic lymph nodes.