02 BOOK OF ABSTRACTS .indd

Proteases and their inhibitors during tumoral
angiogenesis: lessons from knock out mice
Agnes Noel
Laboratory of Tumor and Development Biology, University of Liège, Sart Tilman, Belgium
Pathological angiogenesis are associated with extracellular matrix remodelling and
involve various proteases such as the plasminogen (Plg)/plasminogen activator
(PA) system and matrix metalloproteinases (MMPs). The specific functions of
individual proteases and their inhibitors as anti- or pro-angiogenic mediators remain
to be elucidated. Proteases and their inhibitors are believed to play a key role
in pathological angiogenesis by mediating extracellular matrix degradation, by
shedding cell surface molecules and/or controlling the biological activity of growth
factors, angiogenic factors, chemokines and/or cytokines. Recent findings revealed
paradoxical functions of proteases and their inhibitors. We assessed the impact of
single or combined MMP deficiencies, or single inhibitor deficiency in in vivo and
in vitro models of angiogenesis: (1) tumoral angiogenesis induced by malignant
keratinocyte transplantation, (2) choroidal neoangiogenesis induced by a laser burn
and mimicking the age-related macular degeneration (AMD), and (3) the aortic ring
assay.
Our recent findings highlight the importance of gelatinases (MMP-2 and MMP-9),
membrane type MMPs (MT1-MMP and MT4-MMP) and the inhibitor of plasminogen
activator-1 (PAI-1) as positive regulator of pathological angiogenesis. In sharp
contrast, MMP-19 appears as a negative regulators of tumoral angiogenesis. We will
discuss the individual functions of proteases and their inhibitor during sprouting
angiogenesis, vasculogenesis and lymphangiogenesis. The dissection of the molecular
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mechanisms of action of these proteolytic systems is mandatory to develop new
anti-angiogenic strategies.
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