Open AccessConstitutive Release of Metalloproteinase-9 (92-kd Type IV Collagenase) by Kaposi's Sarcoma Cells
Author(s) -
D. Blankaert,
Th. Simonart,
J. P. Van Vooren,
Dominique Parent,
Corinne Liesnard,
Claire-Michèle Farber,
Thierry Marique,
John Wérenne
Publication year - 1998
Publication title -
journal of acquired immune deficiency syndromes and human retrovirology
Language(s) - English
Resource type - Journals
eISSN - 2331-6993
pISSN - 1077-9450
DOI - 10.1097/00042560-199807010-00002
Subject(s) - collagenase , angiogenesis , matrix metalloproteinase , interstitial collagenase , cell culture , umbilical vein , metalloproteinase , cytokine , tumor necrosis factor alpha , chemistry , cancer research , microbial collagenase , microbiology and biotechnology , in vitro , biology , endocrinology , immunology , enzyme , biochemistry , genetics
Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferating spindle-shaped cells, angiogenesis, and inflammatory cell infiltration. Several lines of evidence suggest that KS is a multifocal cytokine-mediated disease of vascular origin. Because metalloproteinases (MMPs) are important enzymes involved in angiogenesis, we studied their activity in five different KS-derived cell lines and compared these data with those obtained with human umbilical vein endothelial 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 phorbol myristate acetate (PMA) or TNF-alpha increased the 72-kd collagenase activity and also induced a 92-kd collagenase activity. By contrast, KS-derived cells constitutively released significant 72- and 92-kd collagenase activities. The basal release of these enzymes by KS cells was further enhanced by TNF-alpha or PMA. Conversely after in vivo exposure to chemotherapy, KS-derived cells showed a downregulation of the 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.