Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Histopathology. 2013 Feb;62(3):414-20. doi: 10.1111/his.12035.
Multidrug resistance (MDR) in B-cell lymphomas still constitutes a major obstacle to the effectiveness of chemotherapy even in the anti-CD20 antibody therapy era. The aim of this study was to investigate the expression of MDR-associated molecules in reactive lymphadenopathy (RL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).
The expression of mRNA for ABC-transporter family genes was determined by real-time RT-PCR in lymph nodes from RL, FL, and DLBCL cases. MDR1 exhibited significantly stronger expression in RL, FL, and DLBCL than Raji B-cell lymphoma cells. RL and FL showed significantly higher expression than DLBCL. Immunohistochemically, MDR1 positive cells were localized in the germinal centers of RL and center of the nodular lesions of FL showing associations with CD21 positive follicular dendritic cells (FDCs). Raji cells were co-cultured with FDC sarcoma-derived cells and the expression of MDR1 and drug resistance were analyzed. The co-culture of Raji cells with FDCs induced strong expression of MDR1 and introduced resistance to doxorubicin-induced apoptosis.
These results suggest that FDCs induce MDR1 expression in reactive as well as neoplastic B-cells. Inhibition of the interaction of FDCs with B-cells may provide a novel strategy for treating the chemotherapy resistant fraction.
即使在抗 CD20 抗体治疗时代，B 细胞淋巴瘤的多药耐药（MDR）仍然是化疗有效性的主要障碍。本研究旨在研究反应性淋巴结病（RL）、滤泡性淋巴瘤（FL）和弥漫性大 B 细胞淋巴瘤（DLBCL）中与 MDR 相关的分子的表达。
通过实时 RT-PCR 测定 RL、FL 和 DLBCL 病例淋巴结中 ABC 转运蛋白家族基因的 mRNA 表达。MDR1 在 RL、FL 和 DLBCL 中的表达明显强于 Raji B 细胞淋巴瘤细胞。RL 和 FL 的表达明显高于 DLBCL。免疫组化显示，MDR1 阳性细胞定位于 RL 的生发中心和 FL 的结节病变中心，与 CD21 阳性滤泡树突状细胞（FDC）有关。将 Raji 细胞与 FDC 肉瘤衍生细胞共培养，并分析 MDR1 的表达和耐药性。Raji 细胞与 FDC 的共培养诱导了 MDR1 的强烈表达，并引入了对阿霉素诱导凋亡的耐药性。
这些结果表明，FDC 诱导反应性和肿瘤性 B 细胞中 MDR1 的表达。抑制 FDC 与 B 细胞的相互作用可能为治疗化疗耐药部分提供一种新的策略。
