Expression of matrix metalloproteinase-2 in glial and neuronal tumor cell lines: inverse correlation with proliferation rate

The expression of matrix metalloproteinases (MMPs) has been found to be pos itively correlated to the degree of malignancy in gliomas, indicating that poorly differentiated brain tumor cells produce more MMPs than differentiat ed ones, We determined the production of active MMP-2 in five glial (U138MG , U373MG, A172, C6, GOS-3), two neuronal (SK-N-SH, SK-N-MC), and two plurip otent cell lines with facultative neuronal and glial differentiation (P19 a nd NT2) by gelatin zymography. The MMP-2 activity profiles were compared to the proliferative activities of the cell lines. MMP-2 expression varied fr om barely existent (P19 cells) to strong (U138MG and SK-N-SH). Interestingl y, for the cell lines with high MMP-2 expression levels, low proliferative activities were recorded, and vice versa. Retinoic acid induced neuronal di fferentiation and a reduction of proliferation of P19 cells; the differenti ated cells produced significantly more MMP-2 than untreated cells. Upon con fluency, GOS-3 cells showed reduced proliferation, but increased MMP expres sion. Thus, proliferative activity was inversely correlated to MMP-2 expres sion in the tumor cell lines analyzed. (C) 2000 Elsevier Science Ireland Lt d. All rights reserved.