School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
Pathol Int. 2012 Jul;62(7):463-70. doi: 10.1111/j.1440-1827.2012.02823.x. Epub 2012 Apr 20.
Glioblastomas are associated with high mortality due to their aggressive growth and invasiveness. Interactions and functional cross-talk between tumor cells and their microenvironments are mediated by cell surface receptors that are responsible for cell-cell and cell-extracellular matrix adhesion. Central nervous tissues contain plenty of the glycosaminoglycan hyaluronan, and glioma cells express the major cell surface hyaluronan receptor, CD44. In this study, we analyzed the expression and roles of CD44 in human brain tissues. Normal brain tissues showed no or weak CD44 expression, while reactive astrocytes and astrocytoma cells expressed CD44 at variable levels. Immunohistochemically, a higher percentage and intensity of CD44-positive tumor cells were detected in high-grade astrocytomas compared with low-grade astrocytomas. Glioblastoma cells that express CD44 were localized in perivascular and perinecrotic lesions. The human glioma cell lines A172 and KG-1-C expressed CD44 mRNA and protein. Administration of monoclonal anti-human-CD44 antibody inhibited the migration of A172 cells, which are glioblastoma-derived, but did not affect cell growth. In conclusion, CD44 expression levels correlated with the histopathological grade of gliomas, and monoclonal anti-CD44 antibody inhibited the migration of glioblastoma cells. These findings suggest that CD44 is a potential therapeutic target of glioblastomas.
脑胶质瘤由于其侵袭性生长和侵袭性而导致死亡率高。肿瘤细胞与其微环境之间的相互作用和功能串扰是由细胞表面受体介导的,这些受体负责细胞-细胞和细胞-细胞外基质的黏附。中枢神经系统含有大量的糖胺聚糖透明质酸,而神经胶质瘤细胞表达主要的细胞表面透明质酸受体 CD44。在这项研究中,我们分析了 CD44 在人脑组织中的表达和作用。正常脑组织无或弱表达 CD44,而反应性星形胶质细胞和星形细胞瘤细胞以不同的水平表达 CD44。免疫组化分析显示,与低级别星形细胞瘤相比,高级别星形细胞瘤中 CD44 阳性肿瘤细胞的比例和强度更高。表达 CD44 的神经胶质瘤细胞定位于血管周围和坏死周围病变部位。人神经胶质瘤细胞系 A172 和 KG-1-C 表达 CD44 mRNA 和蛋白。单克隆抗人 CD44 抗体的给药抑制了来源于神经胶质瘤的 A172 细胞的迁移,但不影响细胞生长。总之,CD44 的表达水平与神经胶质瘤的组织病理学分级相关,而单克隆抗 CD44 抗体抑制了神经胶质瘤细胞的迁移。这些发现表明 CD44 是神经胶质瘤的一个潜在治疗靶点。