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首页> 外文期刊>British Journal of Haematology >A rare fraction of drug-resistant follicular lymphoma cancer stem cells interacts with follicular dendritic cells to maintain tumourigenic potential
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A rare fraction of drug-resistant follicular lymphoma cancer stem cells interacts with follicular dendritic cells to maintain tumourigenic potential

机译：罕见的耐药性滤泡性淋巴瘤癌症干细胞与滤泡性树突状细胞相互作用，以维持致瘤性潜力

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Follicular lymphoma (FL) comprises nearly 25% of non-Hodgkin lymphoma cases and is clinically characterized by initial sensitivity to chemotherapy followed by relapse. FL stroma contains a special type of stromal cell found in the germinal centre of lymph nodes-the follicular dendritic cell (FDC). We first isolated tumourigenic cells from the FL cell line FLK-1 by side population (SP) technique, and found that SP cells, which express ABCG2, were enriched by chemotherapy and radiation treatments. In vitro, SP cells were attracted by and adhered to FDCs through chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 (CXCL12/CXCR4) signalling. In vivo, limiting dilution assays showed SP cells were highly enriched in cancer stem cells (CSC), but required FDC for tumour formation in non-obese diabetic/severe combined immunodeficiency mice. Treatment with AMD3100, a specific CXCL12/CXCR4 inhibitor, eliminated tumour growth. These findings were then verified with FL cells isolated from an FL patient's ascitic fluid (FLA-1). Finally, we detected the ABCG2 expressing lymphoma cells in FL clinical specimens. Thus, we found that the highly tumourigenic FL cells having CSC-like activities (FL-SC) interact with FDCs in a CXCL12/CXCR4 dependent manner to resist chemotherapy. Our results indicate the importance of FL-SC and niche cell signalling in maintaining tumourigenicity. These signals represent novel targets for CSC eradication.
机译：滤泡性淋巴瘤（FL）占非霍奇金淋巴瘤病例的近25％，其临床特征是对化疗具有初始敏感性，然后复发。 FL基质含有一种在淋巴结生发中心发现的特殊类型的基质细胞-滤泡树突状细胞（FDC）。我们首先通过侧群（SP）技术从FL细胞系FLK-1中分离了致肿瘤细胞，并发现表达ABCG2的SP细胞通过化学疗法和放射疗法得到了富集。在体外，SP细胞通过趋化因子（C-X-C主题）配体12 /趋化因子（C-X-C主题）受体4（CXCL12 / CXCR4）信号吸引并粘附于FDC。在体内，有限稀释试验显示SP细胞高度富集于癌干细胞（CSC）中，但在非肥胖/严重合并免疫缺陷小鼠中肿瘤形成需要FDC。使用AMD3100（一种特定的CXCL12 / CXCR4抑制剂）进行治疗，可以消除肿瘤的生长。然后用从FL患者腹水（FLA-1）中分离出的FL细胞验证了这些发现。最后，我们在FL临床标本中检测到了表达ABCG2的淋巴瘤细胞。因此，我们发现具有CSC样活性（FL-SC）的高度致瘤性FL细胞以CXCL12 / CXCR4依赖性方式与FDC相互作用以抵抗化学疗法。我们的结果表明，FL-SC和小生境细胞信号传导在维持致瘤性方面的重要性。这些信号代表了根除CSC的新靶标。

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