Polysialic acid facilitates tumor invasion by glioma cells
Polysialic acid facilitates tumor invasion by glioma cells
复制标题
DOI：
10.1093/glycob/cwi071
复制
发表时间：
2005-09-01
期刊：
影响因子：
4.3
通讯作者：
Fukuda, M
中科院分区：
文献类型：
--
作者：
Suzuki, M;Suzuki, M;Fukuda, M
聚唾液酸（PSA）被认为可以减弱神经细胞粘附分子（NCAM）的粘附，从而促进神经细胞迁移和再生。虽然PSA的表达已被证明与某些肿瘤（如小细胞肺癌）的进展相关，但尚未有研究确定PSA在神经胶质瘤（人类最常见的原发性脑肿瘤类型）中的作用。在这项研究中，我们首次发现，在神经胶质瘤患者中，PSA更频繁地在弥漫性星形细胞瘤细胞中检测到，这些细胞广泛扩散。为了直接确定PSA在胶质瘤细胞侵袭中的作用，我们用多聚唾液酸转移酶转染C6胶质瘤细胞以表达PSA。在那些转染的细胞中，PSA主要附着于NCAM-140，而模拟转染的C6细胞表达等量的无PSA的NCAM-140。PSA阴性和阳性C6细胞系在体外测得的生长速率几乎相同。然而，PSA阳性C6细胞表现出对胼胝体的侵袭增加，其中模拟转染的C6胶质瘤细胞接种到脑中时很少侵袭。相反，在NCAM缺陷小鼠中观察到模拟转染和PSA阳性C6细胞对胼胝体的侵袭。这些结果综合表明，PSA促进脑胶质瘤的肿瘤侵袭，并且NCAM-NCAM相互作用可能在PSA介导的肿瘤侵袭中减弱。
Polysialic acid (PSA) is thought to attenuate neural cell adhesion molecule (NCAM) adhesion, thereby facilitating neural cell migration and regeneration. Although the expression of PSA has been shown to correlate with the progression of certain tumors such as small cell lung carcinoma, there have been no studies to determine the roles of PSA in gliomas, the most common type of primary brain tumor in humans. In this study, we first revealed that among patients with glioma, PSA was detected more frequently in diffuse astrocytoma cells, which spread extensively. To determine directly the role of PSA in glioma cell invasion, we transfected C6 glioma cells with polysialyltransferases to express PSA. In those transfected cells, PSA is attached mainly to NCAM-140, whereas the mock-transfected C6 cells express equivalent amounts of PSA-free NCAM-140. Both PSA negative and positive C6 cell lines exhibited almost identical growth rates measured in vitro. However, PSA positive C6 cells exhibited increased invasion to the corpus callosum, where the mock-transfected C6 glioma cells rarely invaded when inoculated into the brain. By contrast, the invasion to the corpus callosum by both the mock-transfected and PSA positive C6 cells was observed in NCAM-deficient mice. These results combined indicate that PSA facilitates tumor invasion of glioma in the brain, and that NCAM-NCAM interaction is likely attenuated in the PSA-mediated tumor invasion.