The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells

Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent end opeptidases that are capable of degrading various components of the extrace llular matrix. These enzymes have been implicated in a variety of physiolog ical and pathological conditions including embryogenesis and tumour invasio n. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed by gliomas [epidermal growt h factor (EGF), basic growth factor (bFGF), transforming growth factor beta (TGF-PI,2) and vascular endothelial growth factor (VEGF)].on MMP-2 and MMP -9 expression in an ependymoma, two grade III astrocytomas, a grade III oli goastrocytoma and a benign meningioma. Zymogram analysis revealed that the effects of the growth factors depended upon the cell lines used in the stud y. Growth factors generally up-regulated MMP-2 and MMP-9 expression in the gliomas but were least effective in the meningioma; the effect being most p rominent with TGF-beta 1 and TGF-beta 2 in all the cell lines. It is hypoth esized that paracrine growth factor interplay may be crucial in the regulat ion of MMP expression by glioma invasion of the normal brain. (C) 2000 Canc er Research Campaign.