Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: relation to invasion

In the present work, we analyzed the expression of two major components of the extracellular matrix (ECM), laminin and fibronectin and of two related matrix-metalloproteinases, MMP-2 and MMP-9, in three human glioma cell line s (8 MG, 42 Mg and GL-15) in relation with their differential invasive prop erties. Immunocytochemistry and Western-blots assays indicated the presence of a 200 kDa laminin, similarly expressed in the three cell lines but unde tectable in their ECM. In the opposite, a 230 kDa fibronectin, detected in the three cell lines was differently expressed and only observed in the ECM of the less invasive 8 and 42 MG cells. MMP-2 mRNA analyzed by Northern bl ots and proMMP-2, evaluated by zymography, were found in the three cell lin es but were both ten times higher in the most invasive GL-15 cells. In addi tion, the active form of MMP-2 was only found in the GL-15 cells. In the op posite, the expression of specific tissular inhibitor (TIMP)-2, an endogeno us MMP-2 inhibitor, was restricted to the less invasive cells. MM P-9 activ ity was detected only in the 8 and 42 MG cells and may not be directly invo lved in invasion. Taken together, these results indicate that a high MMP-2/ TIMP-2 ratio may be responsible for the absence of extracellular fibronecti n, underlining the participation of tumour cells in the proteolytic degrada tion of the ECM. An unbalanced MMP-2/TIMP-2 ratio in the micro-environment of malignant cells may contribute to their invasive properties. (C) 2001 El sevier Science Ireland Ltd. All rights reserved.