Stromal cells in lymph nodes attract B-lymphoma cells via production of stromal cell-derived factor-1
Stromal cells in lymph nodes attract B-lymphoma cells via production of stromal cell-derived factor-1
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DOI：
10.1034/j.1600-0609.2000.90147.x
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发表时间：
2000-05-01
影响因子：
3.1
通讯作者：
Fujita, S
中科院分区：
文献类型：
--
作者：
Arai, J;Yasukawa, M;Fujita, S
基质细胞衍生因子-1(SDF-1)是一种由骨髓基质细胞产生的趋化因子，在B淋巴细胞的生成和造血干细胞向骨髓的归巢中发挥重要作用。在本研究中，我们研究了SDF-1及其受体CXCR4在非霍奇金B淋巴瘤细胞与淋巴结基质细胞之间的趋化作用中的作用。SDF-1mRNA在恶性淋巴瘤患者淋巴组织分离的基质细胞中大量表达。所有新鲜从这些患者和大多数实验室B淋巴瘤细胞系分离的B淋巴瘤细胞，包括滤泡性、弥漫性大细胞和Burkitt淋巴瘤细胞，都表达表面CXCR4，并在重组人SDF-1α存在下迁移。趋化实验表明，CXCR4阳性(而不是CXCR4阴性)的B-淋巴瘤细胞向淋巴结基质细胞迁移，这种迁移几乎完全被抗CXCR4单抗或抗SDF-1中和抗体抑制。在向基质细胞迁移的B淋巴瘤细胞中检测到表面CXCR4的下调，而在那些没有迁移反应的B淋巴瘤细胞中检测到下调。此外，淋巴瘤细胞与间质细胞的接触导致淋巴瘤细胞表面CXCR4表达下调。这些数据有力地表明SDF-1/CXCR4是参与B淋巴瘤细胞与淋巴结基质细胞之间趋化作用的主要趋化因子系统。
Stromal cell-derived factor-1 (SDF-1) is a chemokine produced by bone marrow stromal cells which plays an important role in B-lymphopoiesis and the homing of hematopoietic stem cells to the bone marrow. In the present study, we investigated the role of SDF-1 and its receptor, CXCR4, in the chemotactic interaction between non-Hodgkin B-lymphoma cells and lymph node stromal cells. SDF-1 mRNA was abundantly expressed in stromal cells isolated from the lymph nodes of patients with malignant lymphoma. All B-lymphoma cells freshly isolated from these patients and most laboratory B-lymphoma cell lines, including follicular, diffuse large, and Burkitt's lymphoma cells, expressed surface CXCR4 and migrated in the presence of recombinant human SDF-1 alpha. Chemotaxis assays revealed that CXCR4-positive (but not CXCR4-negative) B-lymphoma cells migrated towards lymph node stromal cells, and this migration was almost completely inhibited by the addition of anti-CXCR4 monoclonal antibody to the lymphoma cells or of anti-SDF-1 neutralizing antibody to the culture supernatant of the stromal cells. Down-regulation of surface CXCR4 was detected in B-lymphoma cells which migrated towards the stromal cells but not in those which showed no migratory response. In addition, contact between the lymphoma cells and the stromal cells resulted in down-regulation of surface CXCR4 on the lymphoma cells. These data strongly suggest that SDF-1/CXCR4 is the main chemokine system involved in the chemotactic interaction between B-lymphoma cells and lymph node stromal cells.