Hyaluronate receptors mediating glioma cell migration and proliferation
Hyaluronate receptors mediating glioma cell migration and proliferation
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DOI：
10.1023/a:1012297132047
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发表时间：
2001-01-01
影响因子：
3.9
通讯作者：
Rutka, JT
中科院分区：
文献类型：
--
作者：
Akiyama, Y;Jung, S;Rutka, JT
中枢神经系统（CNS）的细胞外基质（ECM）富含透明质酸（HA）。HA的普遍受体是CD44和HA介导的运动受体RHAMM。在本研究中，我们研究了CD44和RHAMM在人类星形细胞瘤细胞迁移和增殖中的潜在作用。采用免疫细胞化学和western blot方法检测ha受体在脑肿瘤细胞系和手术标本中的表达。RHAMM结合配体的能力是通过脑肿瘤裂解物的十六烷基氯化吡啶（CPC）沉淀在ha结合试验中确定的。采用MTT法和迁移法测定HA、CD44阻断抗体和RHAMM可溶性肽对星形细胞瘤细胞生长和迁移的影响。我们的研究结果表明，ha受体CD44和RHAMM的表达在胶质瘤细胞系和胶质瘤标本中几乎普遍存在。在胶质瘤中有表达梯度，高级别胶质瘤比低级别病变或正常人类星形胶质细胞或人脑非肿瘤标本表达更多的RHAMM和CD44。在CPC沉淀后，85和58 kda大小的特异性RHAMM变体被证明与HA紧密结合。RHAMM可溶性肽以剂量依赖性方式抑制胶质瘤细胞系增殖。最后，虽然抗cd44抗体不抑制人类胶质瘤细胞的迁移，但针对RHAMM的ha结合区域的可溶性肽抑制胶质瘤在HA-based ECM上和下的迁移。这些数据支持ha受体参与脑肿瘤粘附、增殖和迁移的观点，在找到更有效的治疗策略之前，必须更好地了解这些生物学特征。
The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.