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 lines (8 MG, 42 Mg and GL-15) in relation with their differential invasive properties. Immunocytochemistry and Western-blots assays indicated the presence of a 200 kDa laminin, similarly expressed in the three cell lines but undetectable 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 blots and proMMP-2, evaluated by zymography, were found in the three cell lines but were both ten times higher in the most invasive GL-15 cells. In addition, the active form of MMP-2 was only found in the GL-15 cells. In the opposite, the expression of specific tissular inhibitor (TIMP)-2, an endogenous MMP-2 inhibitor, was restricted to the less invasive cells. MMP-9 activity was detected only in the 8 and 42 MG cells and may not be directly involved in invasion. Taken together, these results indicate that a high MMP-2/TIMP-2 ratio may be responsible for the absence of extracellular fibronectin, underlining the participation of tumour cells in the proteolytic degradation of the ECM. An unbalanced MMP-2/TIMP-2 ratio in the micro-environment of malignant cells may contribute to their invasive properties.
Planchenault
T
T
GERMEN, Medical Faculty, Paris XII, France.
Costa
S
S
Fages
C
C
Riche
D
D
Charrière-Bertrand
C
C
Perzelova
A
A
Barlowatz-Meimon
G
G
Tardy
M
M
D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D005353:Fibronectins; D007797:Laminin; D019716:Tissue Inhibitor of Metalloproteinase-2; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2