Exploitation of Astrocytes by Glioma Cells to Facilitate Invasiveness: A Mechanism Involving Matrix Metalloproteinase-2 and the Urokinase-Type Plasminogen Activator–Plasmin Cascade

摘要: The presence of reactive astrocytes around glioma cells in the CNS suggests possibility that these two cell types could be interacting. We addressed whether use astrocyte environment to modulate matrix metalloproteinase-2 (MMP-2), a proteolytic enzyme implicated invasiveness cells. found culture produce significant amounts pro-form MMP-2 but undetectable levels active MMP-2. However, after coculture with U251N line, pro-MMP-2 was converted form. mechanism activation glioma-astrocyte investigated and involve urokinase-type plasminogen activator (uPA)-plasmin cascade whereby uPA bound receptor (uPAR), leading conversion plasmin. latter cleaved generate its Furthermore, key components (i.e., uPAR, uPA, pro-MMP-2) were contributed principally by astrocytes, whereas provided plasminogen. In correspondence this biochemical cascade, transmigration through Boyden invasion chambers coated an extracellular barrier increased significantly inhibited agents disrupted uPA-plasmin cascade. Finally, using resected human glioblastoma specimens, we tumor cells, not expressed situ. conclude exploit their activate leads