Study on CXCR4/SDF-1α axis in lymph node metastasis of cervical squamous cell carcinoma

Study on CXCR4/SDF-1α axis in lymph node metastasis of cervical squamous cell carcinoma
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DOI:
10.1111/j.1525-1438.2007.00786.x
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发表时间:
2007-03-01
影响因子:
4.8
通讯作者:
Xie, X.
Xie, X.
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, J. -P.;Lu, W. -G.;Xie, X.

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CXCR4/基质细胞衍生因子-1α(SDF-1α)参与多种肿瘤转移机制。用CXCR4单抗对35例宫颈鳞癌组织、10例正常宫颈组织、10例转移淋巴结和50例Hela细胞进行免疫组织化学染色。同时用兔抗SDF-1α进行免疫组织化学染色。用Transwell可渗透载体(Corning,NY)评价Hela细胞的体外侵袭能力,将含/不含CXCR4单抗的Hela细胞接种于上室,在下室加入含有0~100 ng/mLSDF-1α的培养液。为探讨CXCR4/SDF-1α对宫颈癌细胞增殖的影响,将CXCR4/SDF-1α与CXCR4单抗共同作用于Hela细胞72 h。我们发现CXCR4在所有宫颈癌、转移淋巴结和Hela细胞的SCC细胞上都有表达,而在正常宫颈组织中不表达。SDF-1α在所有淋巴结的淋巴细胞上均有表达。SDF-1α以浓度依赖方式诱导Hela细胞的定向迁移,CXCR4单抗可抑制SDF-1α诱导的Hela细胞定向迁移(P<0.05)。SDF-1α还可刺激CXCR4介导的Hela细胞增殖(P<0.05)。CXCR4/SDF-1α轴可能参与了宫颈癌的淋巴转移。
CXCR4/stromal-cell-derived factor-1 alpha (SDF-1 alpha) 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-1 alpha. 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-1 alpha was added to the lower compartments. For evaluating the effect of CXCR4/SDF-1 alpha on proliferation of cervical cancer cells, Hela cells were cultured for 72 h exposed to SDF-1 alpha 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-1 alpha was expressed on lymph cells in all lymph nodes. SDF-1 alpha induced the directed migration of Hela cells with a concentration-dependent model, which was inhibited by CXCR4 mAb (P < 0.05). SDF-1 alpha also stimulated the proliferation of Hela cells mediated by CXCR4 (P < 0.05). CXCR4/SDF-1 alpha axis probably participates in the metastasis toward lymph nodes in cervical cancer.