title: Mechanisms of kaposis-sarcoma cell supernatant-induced vascular cell invasion.
abstract: Kaposi's sarcoma (KS) is a highly angiogenic lesion frequently associated with acquired immune deficiency syndrome. Histologically the lesions appear to contain proliferative 'spindle shaped' cells with a mixed smooth muscle-endothelial-fibroblastic histotype and a conspicuous neovascularization, derived from host cell recruitment. Media conditioned by cultured KS cells (KS-CM) have angiogenic properties. KS-CM is able to promote endothelial and smooth muscle cell migration and invasion. The mechanisms of this KS-CM activity are still unknown. We hypothesize that KS-CM contains numerous factors with different roles in inducing the neo angiogenic process. We show that AIDS-IST-KS cell supernatants induce gelatinase A production and plasminogen activator (PA) up-regulation in vascular cells. KS-CM activity in vivo is heparin dependent. Also bFGF alone, a heparin dependent factor, alone can induce endothelial and smooth muscle cell invasion, MMP-2 production and PA activity. 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. Chromatography of KS-CM on heparin-sepharose demonstrates the presence of two heparin-binding fractions with chemotactic and gelatinase A inducing activity. The flow through was also active. KS-CM absorption on heparin-sepharose beads did not modify its induction of PA activity, further evidence for the presence of non heparin-binding factors as well.
authors.affiliation: IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,I-16132 GENOA,ITALY. UNIV BRESCIA,DEPT BIOCHEM SCI & BIOTECHNOL,GEN PATHOL UNIT,I-25123 BRESCIA,ITALY.
authors.forename: D
authors.initials: D
authors.lastname: Giunciuglio
authors.forename: R
authors.initials: R
authors.lastname: Benelli
authors.forename: L
authors.initials: L
authors.lastname: Masiello
authors.forename: I
authors.initials: I
authors.lastname: Paglieri
authors.forename: A
authors.initials: A
authors.lastname: Pesarini
authors.forename: M
authors.initials: M
authors.lastname: Presta
authors.forename: D
authors.initials: D
authors.lastname: Noonan
authors.forename: A
authors.initials: A
authors.lastname: Albini