Zhang Chun, Cui Guo-Hui, Liu Fang, Wu Qiu-Ling, Chen Yan
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Yi Xue Za Zhi. 2007 Mar 13;87(10):695-7.
To study the expression of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in non-Hodgkin lymphoma (NHL), and to investigate the role of this biological axis in tumor metastasis of NHL.
Specimens of bone marrow were collected from 4 patients with NHL with bone marrow infiltration and 4 cases of NHL without bone marrow infiltration, and 4 patients with benign hepatopathy with normal myelogram. Lymphoma specimens were collected from 7 cases of NHL and 3 cases of reactive proliferative lymphadenitis. The level of SDF-1alpha mRNA in the stromal cells of bone marrow and lymph node were determined by RT-PCR. The CXCR4 expression on lymphoma cells freshly isolated from bone marrow and lymph node of the NHL patients were studied by flow cytometry. Transwell assay was performed, the upper chamber being added with suspension of cells newly isolated from lymph nodes or bone marrow undergoing co-incubation with ant-CXCR4 monoclonal antibody or not, and the lower chamber added with culture fluid with or without recombinant human SDF-1alpha (rhSDF-1alpha). The migration rate of the primary lymphoma cells towards rhSDF-1alpha was calculated.
The expression levels of CXCR4 on the lymphoma cells isolated from the bone marrow involved or not involved by NHL were both significantly higher than that of the mononuclear cells from normal bone marrow (both P < 0.01), whereas the CXCR4 expression level on the lymphoma cells from the lymph nodes of the NHL patients was also significantly higher than that of the mononuclear cells from the lymph nodes of reactive proliferative lymphadenitis (P < 0.01). The SDF-1alpha mRNA expression level in the stromal cells isolated from the bone marrow involved by NHL was significantly higher than those of the stromal cells of bone marrow not involved by NHL and the normal bone marrow (both P < 0.01). Moreover, the SDF-1alpha expression level in the lymph node stromal cells of all the NHL patients was also significantly higher than that of the patients with reactive proliferative lymphadenitis (P < 0.01). Transwell assay revealed that all three kinds of primary lymphoma cells migrated towards rhSDF-1alpha effectively, and this migration was markedly inhibited by the addition of anti-CXCR4 monoclonal antibody to the lymphoma cells (all P < 0.01).
SDF-1/CXCR4 axis plays a uniquely important biological role in mediating tumor metastasis of NHL.
研究基质细胞衍生因子-1（SDF-1）及其受体CXCR4在非霍奇金淋巴瘤（NHL）中的表达情况，并探讨该生物学轴在NHL肿瘤转移中的作用。
收集4例伴有骨髓浸润的NHL患者、4例无骨髓浸润的NHL患者以及4例骨髓象正常的良性肝病患者的骨髓标本。收集7例NHL患者和3例反应性增生性淋巴结炎患者的淋巴瘤标本。采用逆转录-聚合酶链反应（RT-PCR）检测骨髓和淋巴结基质细胞中SDF-1α mRNA的水平。采用流式细胞术研究从NHL患者骨髓和淋巴结中新鲜分离的淋巴瘤细胞上CXCR4的表达情况。进行Transwell实验，上室加入从淋巴结或骨髓中新鲜分离的细胞悬液，分别与抗CXCR4单克隆抗体共同孵育或不孵育，下室加入含或不含重组人SDF-1α（rhSDF-1α）的培养液。计算原代淋巴瘤细胞向rhSDF-1α的迁移率。
从伴有或不伴有骨髓浸润的NHL患者骨髓中分离出的淋巴瘤细胞上CXCR4的表达水平均显著高于正常骨髓单个核细胞（均P<0.01），而NHL患者淋巴结淋巴瘤细胞上CXCR4的表达水平也显著高于反应性增生性淋巴结炎患者淋巴结单个核细胞（P<0.01）。从伴有骨髓浸润的NHL患者骨髓中分离出的基质细胞中SDF-1α mRNA表达水平显著高于无骨髓浸润的NHL患者骨髓基质细胞和正常骨髓基质细胞（均P<0.01）。此外，所有NHL患者淋巴结基质细胞中SDF-1α表达水平也显著高于反应性增生性淋巴结炎患者（P<0.01）。Transwell实验显示，三种原代淋巴瘤细胞均能有效地向rhSDF-1α迁移，而向淋巴瘤细胞中加入抗CXCR4单克隆抗体可显著抑制这种迁移（均P<0.01）。
SDF-1/CXCR4轴在介导NHL肿瘤转移中发挥独特重要的生物学作用。
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