Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS, 90035-003, Brazil.
Mol Cell Biochem. 2012 Jan;359(1-2):315-22. doi: 10.1007/s11010-011-1025-9. Epub 2011 Aug 21.
Glioblastoma multiform is the most common and aggressive type of brain tumor. The overexpression of ecto-5'-nucleotidase/CD73 (ecto-5'-NT/CD73), an adhesion molecule and the main enzymatic source of extracellular adenosine, has been reported in tumor cells, and it is emerging as a component of glioma progression. Here, we evaluated the involvement of ecto-5'-NT/CD73 in cell adhesion through its interaction with different components of the extracellular matrix in the human U138MG glioma cell line. The results indicated that adenosine induced an increase in glioma cell adhesion. The treatment of glioma cells with adenosine receptor antagonists, APCP (α,β-methylene ADP) and dipyridamole prevented the adenosine effect, indicating the participation of extracellular and intracellular signaling pathways in cell adhesion mediated by adenosine. The ECM protein laminin (lam) and chondroitin sulfate (ChS) modulated the ecto-5'-NT/CD73 activity and glioma adhesion in a parallel manner, suggesting the involvement of purinergic signaling in the effects mediated by the extracellular matrix. Taken together, these results suggest that ecto-5'-NT/CD73, an important producer of extracellular adenosine, may modulate glioma cell adhesion and tumor cell-extracellular matrix interactions.
胶质母细胞瘤是最常见和侵袭性最强的脑肿瘤。在肿瘤细胞中已经报道了ecto-5'-核苷酸酶/CD73(ecto-5'-NT/CD73)的过度表达,ecto-5'-NT/CD73 是一种黏附分子和细胞外腺苷的主要酶源,并且它作为神经胶质瘤进展的组成部分而出现。在这里,我们通过其与人类 U138MG 神经胶质瘤细胞系中细胞外基质的不同成分相互作用,评估了ecto-5'-NT/CD73 在细胞黏附中的参与。结果表明,腺苷诱导神经胶质瘤细胞黏附增加。用腺苷受体拮抗剂 APCP(α,β-亚甲基 ADP)和双嘧达莫处理神经胶质瘤细胞可防止腺苷的作用,表明细胞外和细胞内信号通路参与了由腺苷介导的细胞黏附。细胞外基质蛋白层粘连蛋白(lam)和软骨素硫酸盐(ChS)以平行的方式调节ecto-5'-NT/CD73 活性和神经胶质瘤黏附,表明嘌呤能信号转导参与了细胞外基质介导的作用。总之,这些结果表明,ecto-5'-NT/CD73 是细胞外腺苷的重要产生者,可能调节神经胶质瘤细胞黏附和肿瘤细胞-细胞外基质相互作用。