Turley E A, Belch A J, Poppema S, Pilarski L M
Manitoba Institute for Cell Biology, University of Manitoba, Canada.
Blood. 1993 Jan 15;81(2):446-53.
Migration through extracellular matrix is fundamental to malignant invasion. A receptor for hyaluronan-mediated motility (RHAMM) has previously been shown to play a fundamental role in locomotion of ras-transformed cells as well as functioning in signal transduction. Expression of RHAMM was characterized on B lymphocytes from normal and malignant lymphoid tissues using multiparameter phenotypic immunofluorescence analysis as well as functional analysis of its role in locomotion of malignant hairy cell leukemia B cells. RHAMM is not detectable on most normal B cells located in blood, spleen, or lymph node, but it is detectable on bone marrow and thymic B cells. Among B-cell malignancies, it is expressed on most terminally differentiated B cells from multiple myeloma bone marrows, is present on a subset of non-Hodgkin's lymphomas, and is absent on B chronic lymphocytic leukemia. Activation of peripheral blood B cells by Staphylococcus A cowan (SAC), but not by pokeweed mitogen, induced transient expression of RHAMM at day 3 of culture, suggesting RHAMM may be used by antigen-activated normal B cells. For malignant cells, expression of RHAMM increased on long-term culture of bone marrow plasma cells from multiple myeloma patients, indicating prolonged expression in contrast to the transient expression on SAC-activated normal B cells. Intriguingly, RHAMM was expressed on hairy leukemia cells located in spleen but absent from those in peripheral blood of the same patient. RHAMM, as expressed on splenic hairy cells, was a 58-Kd molecule that binds hyaluronan, is encoded by a 5.2-kb messenger RNA, and participates in locomotion by these cells. Hairy cells locomoted in response to hyaluronan at 4 mu per minute. Monoclonal antibody to RHAMM inhibited this locomotion almost completely as detected using video time-lapse cinemicrography. These observations are consistent with a role for RHAMM in malignant invasion and metastatic growth.
通过细胞外基质迁移是恶性侵袭的基础。透明质酸介导的运动受体（RHAMM）先前已被证明在ras转化细胞的运动中起重要作用，并在信号转导中发挥功能。使用多参数表型免疫荧光分析以及其在恶性毛细胞白血病B细胞运动中的作用的功能分析，对来自正常和恶性淋巴组织的B淋巴细胞上的RHAMM表达进行了表征。在血液、脾脏或淋巴结中的大多数正常B细胞上检测不到RHAMM，但在骨髓和胸腺B细胞上可以检测到。在B细胞恶性肿瘤中，它在多发性骨髓瘤骨髓中大多数终末分化的B细胞上表达，在一部分非霍奇金淋巴瘤中存在，而在B慢性淋巴细胞白血病中不存在。用金黄色葡萄球菌A株（SAC）而非商陆有丝分裂原激活外周血B细胞，可在培养第3天诱导RHAMM的瞬时表达，提示抗原激活的正常B细胞可能利用RHAMM。对于恶性细胞，多发性骨髓瘤患者骨髓浆细胞长期培养时RHAMM表达增加，表明与SAC激活的正常B细胞的瞬时表达相比，其表达持续时间延长。有趣的是，RHAMM在位于脾脏的毛细胞白血病细胞上表达，但在同一患者外周血中的毛细胞白血病细胞上不表达。脾脏毛细胞上表达的RHAMM是一种58-kD的分子，可结合透明质酸，由5.2-kb的信使RNA编码，并参与这些细胞的运动。毛细胞对透明质酸的反应速度为每分钟4微米。使用视频延时电影显微镜检测发现，针对RHAMM的单克隆抗体几乎完全抑制了这种运动。这些观察结果与RHAMM在恶性侵袭和转移生长中的作用一致。
