CONSTITUTIVE RELEASE OF METALLOPROTEINASE-9 (92-KD TYPE-IV COLLAGENASE) BY KAPOSIS-SARCOMA CELLS

Kaposi's sarcoma (KS) is an angioproliferative disease characterized b y proliferating spindle-shaped cells, angiogenesis, and inflammatory c ell infiltration. Several lines of evidence suggest that KS is a multi focal cytokine-mediated disease of vascular origin. Because metallopro teinases (MMPs) are important enzymes involved in angiogenesis, we stu died their activity in five different KS-derived cell lines and compar ed these data with those obtained with human umbilical vein endothelia l cells (HUVEC). We focused on the activity of the 72- and 92-kd type IV collagenases because these enzymes are thought to play an important role in the process of tumoral invasion. Nonstimulated HUVEC released a weak 72-kd collagenase activity and no 92-kd collagenase activity, as determined by zymographic analysis. Stimulation of HUVEC with phorb ol myristate acetate (PMA) or TNF-alpha increased the 72-kd collagenas e activity and also induced a 92-kd collagenase activity. By contrast, KS-derived cells constitutively released significant 72- and 92-kd co llagenase activities. The basal release of these enzymes by KS cells w as further enhanced by TNF-alpha or PMA. Conversely, after in vivo exp osure to chemotherapy, KS-derived cells showed a down-regulation of th e production of MMPs that could be reversed by the addition of TNF or PMA. These results suggest that KS cells have constitutive features of activated cells that have an invasive and metastasizing potential.