Mechanisms of Kaposi's sarcoma cell supernatant-induced vascular cell invasion

D. Giunciuglio, R. Benelli, L. Masiello, I. Paglieri, A. Pesarini, M. Presta, D. M. Noonan, A. Albini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalInternational Journal of Oncology
Volume6
Issue number3
Publication statusPublished - 1995

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Keywords

  • angiogenesis
  • growth factors
  • Kaposi
  • proteases
  • vascular cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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