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Plasma Membrane-Dependent Activation of Gelatinase a in Human Vascular Endothelial Cells
Lewalle, J. M.; Munaut, Carine; Pichot, B. et al.
1995In Journal of Cellular Physiology, 165 (3), p. 475-83
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Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Lewalle, J. M.
Munaut, Carine  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Pichot, B.
Cataldo, Didier  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques
Baramova, Eugéenia N.
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Language :
English
Title :
Plasma Membrane-Dependent Activation of Gelatinase a in Human Vascular Endothelial Cells
Publication date :
December 1995
Journal title :
Journal of Cellular Physiology
ISSN :
0021-9541
eISSN :
1097-4652
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
165
Issue :
3
Pages :
475-83
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 09 January 2009

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