|Reference : Plasma Membrane-Dependent Activation of Gelatinase a in Human Vascular Endothelial Cells|
|Scientific journals : Article|
|Life sciences : Biochemistry, biophysics & molecular biology|
|Plasma Membrane-Dependent Activation of Gelatinase a in Human Vascular Endothelial Cells|
|Lewalle, J. M. [> > > >]|
|Munaut, Carine [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]|
|Pichot, B. [> > > >]|
|Cataldo, Didier [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques]|
|Baramova, E. [> > > >]|
|Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]|
|Journal of Cellular Physiology|
|Wiley Liss, Inc.|
|Yes (verified by ORBi)|
|[en] The initiation of the angiogenic process requires a locally confined and time-limited proteolysis of the basement membrane (BM) components at the site of new vessel sprout. Gelatinase A, a member of the matrix metalloproteinase family, degrades BM type IV collagen and is involved in the BM breakdown by migrating tumor cells and endothelial cells (EC). Gelatinase A is synthesized as latent proenzyme and must be activated in order to express its proteolytic activity. A plasma membrane-dependent mechanism of activation has been described for several tumor and transformed cells lines. In the present study, we show that latent (72 kD) and mature (62-59 kD) forms of gelatinase A are present in EC membrane fraction from Triton X-114 extract while only latent form is found in the cytosolic fraction. The incubation of EC membrane fraction with exogenous latent gelatinase A resulted in a significant activation giving rise to 62-59 kD mature forms. 12-O-tetradecanoylphorbol-13-acetate (TPA), a strong potentiator of angiogenesis in vitro and in vivo, increases the amount of both latent and activated forms of gelatinase A in EC membrane fraction as well as the ability of this latter fraction to activate exogenous latent gelatinase A. We show that the mRNA transcript coding for the membrane-integrated MMP, the MT-MMP, previously described as a potential gelatinase A activator in invasive tumor cells is also expressed in vascular EC and is regulated through a TPA sensitive process. This enzyme may be responsible for membrane-dependent gelatinase A activation in normal vascular EC and may therefore be a determinant in the control of BM proteolysis during angiogenesis.|
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