Zhang J-P, Lu W-G, Ye F, Chen H-Z, Zhou C-Y, Xie X
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Int J Gynecol Cancer. 2007 Mar-Apr;17(2):478-83. doi: 10.1111/j.1525-1438.2007.00786.x.
CXCR4/stromal-cell-derived factor-1alpha (SDF-1alpha) is involved in many cancer metastatic mechanisms. Cervical squamous cell cancer (SCC) tissues (n=35), normal cervical tissues (n=10), metastatic (n=10) and nonmetastatic lymph nodes (n=50), and Hela cells were stained immunohistochemically with CXCR4 monoclonal antibody (mAb). Meanwhile, lymph nodes were stained immunohistochemically with rabbit anti-SDF-1alpha. In vitro invasion of Hela cells was evaluated using Transwell Permeable Supports (Corning, NY), in which Hela cells with/without CXCR4 mAb preincubation were seeded in the upper chambers and medium containing 0-100 ng/mL SDF-1alpha was added to the lower compartments. For evaluating the effect of CXCR4/SDF-1alpha on proliferation of cervical cancer cells, Hela cells were cultured for 72 h exposed to SDF-1alpha with and without CXCR4 mAb. We found that CXCR4 was expressed on SCC cells in all cervical cancer, metastatic lymph node, and Hela cells but not in normal cervix. SDF-1alpha was expressed on lymph cells in all lymph nodes. SDF-1alpha induced the directed migration of Hela cells with a concentration-dependent model, which was inhibited by CXCR4 mAb (P<0.05). SDF-1alpha also stimulated the proliferation of Hela cells mediated by CXCR4 (P<0.05). CXCR4/SDF-1alpha axis probably participates in the metastasis toward lymph nodes in cervical cancer.
CXCR4/基质细胞衍生因子-1α(SDF-1α)参与多种癌症转移机制。采用CXCR4单克隆抗体(mAb)对35例宫颈鳞状细胞癌(SCC)组织、10例正常宫颈组织、10例转移性和50例非转移性淋巴结以及Hela细胞进行免疫组织化学染色。同时,用兔抗SDF-1α对淋巴结进行免疫组织化学染色。使用Transwell可渗透支持物(康宁公司,纽约)评估Hela细胞的体外侵袭能力,将预先孵育或未预先孵育CXCR4 mAb的Hela细胞接种在上室,在下室中加入含0 - 100 ng/mL SDF-1α的培养基。为评估CXCR4/SDF-1α对宫颈癌细胞增殖的影响,将Hela细胞在有或无CXCR4 mAb存在的情况下暴露于SDF-1α中培养72小时。我们发现CXCR4在所有宫颈癌、转移性淋巴结及Hela细胞的SCC细胞上表达,但在正常宫颈中不表达。SDF-1α在所有淋巴结的淋巴细胞上表达。SDF-1α以浓度依赖模式诱导Hela细胞的定向迁移,这一过程被CXCR4 mAb抑制(P<0.05)。SDF-1α还刺激由CXCR4介导的Hela细胞增殖(P<0.05)。CXCR4/SDF-1α轴可能参与宫颈癌向淋巴结的转移。