MECHANISMS OF KAPOSIS-SARCOMA CELL SUPERNATANT-INDUCED VASCULAR CELL INVASION

Kaposi's sarcoma (KS) is a highly angiogenic lesion frequently associa ted with acquired immune deficiency syndrome. Histologically the lesio ns appear to contain proliferative 'spindle shaped' cells with a mixed smooth muscle-endothelial-fibroblastic histotype and a conspicuous ne ovascularization, derived from host cell recruitment. Media conditione d by cultured KS cells (KS-CM) have angiogenic properties. KS-CM is ab le to promote endothelial and smooth muscle cell migration and invasio n. The mechanisms of this KS-CM activity are still unknown. We hypothe size that KS-CM contains numerous factors with different roles in indu cing the neo angiogenic process. We show that AIDS-IST-KS cell superna tants induce gelatinase A production and plasminogen activator (PA) up -regulation in vascular cells. KS-CM activity in vivo is heparin depen dent. Also bFGF alone, a heparin dependent factor, alone can induce en dothelial and smooth muscle cell invasion, MMP-2 production and PA act ivity. However, antibodies to bFGF do not block KS-CM activity and do not reduce the effect on PA up-regulation. This evidence suggests that heparin-binding factors other than bFGF may be present. Chromatograph y of KS-CM on heparin-sepharose demonstrates the presence of two hepar in-binding fractions with chemotactic and gelatinase A inducing activi ty. The flow through was also active. KS-CM absorption on heparin-seph arose beads did not modify its induction of PA activity, further evide nce for the presence of non heparin-binding factors as well.