Expression of multiple matrix metalloproteinases and urokinase type plasminogen activator in cultured Kaposi sarcoma cells

Kaposi's sarcoma (KS) cells are considered to be of endothelial origin. KS lesions are characterized by hyperproliferation and an invasive phenotype. We have determined that KS cell cultures constitutively secrete multiple fo rms of several matrix metalloproteinases (MMPs) and an altered form of urok inase plasminogen activator (uPA) by zymogram and Western analysis of the c ulture media. MMPs are a family of secreted endoproteinases which degrade c omponents of the extracellular matrix. Their enhanced expression and activi ty are strongly correlated with cellular processes involving tissue remodel ing and invasion. The KS cells secrete increased levels of gelatinase A and B and a high molecular weight uPA in vitro when compared with non-KS endot helial or epithelial cells. Multiple forms of gelatinases A and B were obse rved on gelatin zymograms. Caseinolytic bands observed were confirmed by We stern blot analysis to be due to stromelysin activity, whereas matrilysin w as not detected by casein zymography. Western blot analysis also detected s ecretion of interstitial collagenase and high molecular weight uPA. Gelatin olytic activity with the mobility of gelatinase B was detected on gelatin z ymograms, but not by Western analysis. This unusual constitutive expression pattern of MMPs and uPA by KS cells in vitro is characterized by elevated levels of gelatinase A, gelatinase B, interstitial collagenase, stromelysin and a high molecular weight form of uPA, and the lack of expression of mat rilysin. These secreted MMPs, taken together, are capable of digesting a br oad range of components of the extracellular matrix. This unusual pattern i s likely to contribute to the characteristic hyperproliferative and invasiv e phenotype of KS lesions.