Masellis-Smith A, Belch A R, Mant M J, Turley E A, Pilarski L M
Department of Oncology, University of Alberta, Edmonton, Canada.
Blood. 1996 Mar 1;87(5):1891-9.
We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA-binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA-binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma.
我们研究了多发性骨髓瘤（MM）患者的血液B细胞、骨髓（BM）浆细胞和终末期白血病浆细胞（T-PCL）在细胞外基质蛋白上的迁移能力。通过延时视频显微镜观察发现，透明质酸（HA）而非I型胶原、IV型胶原或层粘连蛋白可促进MM血液B细胞的迁移。13%至20%的MM血液B细胞在HA上迁移，平均速度为19微米/分钟，超过75%的MM血液B细胞表现出活跃的细胞运动和质膜变形，MM患者的循环T-PCL和骨外浆细胞也如此。相比之下，MM患者BM中获得的浆细胞在所有测试底物上均缺乏运动性，且未表现出细胞膜突出或细胞变形。所有检测来源的MM血液B细胞和MM浆细胞均表达HA结合受体——HA介导运动性受体（RHAMM）和CD44。在循环MM B细胞上，RHAMM和CD44均参与HA结合，表明它们在体外以活化构象表达。相反，对于大多数MM患者的大多数BM浆细胞，RHAMM或CD44的表达并未伴随HA结合。少数患者确实有HA结合的BM浆细胞，涉及RHAMM和CD44，这通过用抗RHAMM或抗CD44单克隆抗体（MoAbs）进行部分阻断得以证明。尽管RHAMM和CD44均与HA结合，但MM血液B细胞在HA上的迁移受到抗RHAMM而非抗CD44 MoAbs的抑制，表明是RHAMM而非CD44介导了在HA上的运动性。因此，MM中的循环B细胞和浆细胞表现出依赖RHAMM和HA的运动行为，表明具有迁移潜力，而BM浆细胞是静止的。我们推测循环B细胞或浆细胞的一个亚群介导了骨髓瘤的恶性扩散。
