DEGRADATION OF COLLAGEN TYPE-IV BY C6 ASTROCYTOMA-CELLS

The key event associated with the initiation of angiogenesis is the lo calized degradation of the vascular basement membrane. Because of its complex structure, any remodelling and/or modification of the basement membrane must involve the co-ordinated function of a number of differ ent enzyme systems. Type IV collagen is a major protein component (60- 90%) of the basement membrane and its degradation is crucial to the in itiation of angiogenesis. This study has focused on the mechanisms by which C6 astrocytoma cells degrade human type IV collagen. C6 astrocyt oma cells use components of two major degradative pathways to degrade collagen type IV. The major matrix metalloproteinase identified is the activated form (68-KDa) of gelatinase A (72-KDa matrix metalloprotein ase) and a serine sensitive 1000-KDa collagenase type IV degrading act ivity which appears to have the characteristics of a novel extracellul ar proteasome.