Jourdan M, Ferlin M, Legouffe E, Horvathova M, Liautard J, Rossi J F, Wijdenes J, Brochier J, Klein B
INSERM U475, Montpellier, France.
Br J Haematol. 1998 Mar;100(4):637-46. doi: 10.1046/j.1365-2141.1998.00623.x.
Syndecan-1 is a cell membrane proteoglycan that binds extracellular matrix components and various growth factors. It is expressed only on malignant plasma cells in bone marrow samples from patients with multiple myeloma (MM). Several reports have suggested that syndecan-1 was present only on a part of the myeloma cells. By using either IL-6-dependent myeloma cell lines or primary myeloma cells stained by annexin V, we report here that syndecan-1 was rapidly lost by myeloma cells undergoing apoptosis. In the same experimental conditions, expression of other cell membrane antigens such as CD38, HLA class-I or CD49d on apoptotic myeloma cells was not affected. In addition, we show that syndecan-1 loss was independent of activation of the gp130 IL-6 transducer. Dexamethasone induced a strong apoptosis of myeloma cells associated with the loss of syndecan-1. Finally, by using freshly-explanted tumoural samples, we show that syndecan-1 rapidly disappeared from myeloma cells in association with induction of apoptosis. In conclusion we showed that syndecan-1 is a marker for viable myeloma cells which is rapidly lost by apoptotic cells. These results emphasize the usefulness of anti-syndecan-1 antibodies to purge tumoural cells from haemopoietic grafts or to purify these cells for further manipulations for immuno or gene therapies.
Syndecan-1是一种细胞膜蛋白聚糖,可结合细胞外基质成分和多种生长因子。它仅在多发性骨髓瘤(MM)患者骨髓样本中的恶性浆细胞上表达。有几份报告表明,syndecan-1仅存在于部分骨髓瘤细胞上。通过使用依赖白细胞介素-6的骨髓瘤细胞系或经膜联蛋白V染色的原代骨髓瘤细胞,我们在此报告,正在经历凋亡的骨髓瘤细胞会迅速丢失syndecan-1。在相同的实验条件下,凋亡骨髓瘤细胞上其他细胞膜抗原如CD38、HLA-I类或CD49d的表达不受影响。此外,我们表明syndecan-1的丢失与gp130白细胞介素-6转导器的激活无关。地塞米松诱导骨髓瘤细胞强烈凋亡,并伴有syndecan-1的丢失。最后,通过使用新鲜移植的肿瘤样本,我们表明syndecan-1与凋亡诱导相关,在骨髓瘤细胞中迅速消失。总之,我们表明syndecan-1是存活骨髓瘤细胞的标志物,凋亡细胞会迅速丢失该标志物。这些结果强调了抗syndecan-1抗体在从造血移植物中清除肿瘤细胞或纯化这些细胞以进行免疫或基因治疗的进一步操作中的有用性。